diff --git a/DESCRIPTION b/DESCRIPTION index 263fbee..0b0219c 100644 --- a/DESCRIPTION +++ b/DESCRIPTION @@ -14,3 +14,7 @@ Imports: dplyr, stringr, synthesisr +Suggests: + knitr, + rmarkdown +VignetteBuilder: knitr diff --git a/R/check_retracted.R b/R/check_retracted.R index 2ad8400..6ff6f0b 100644 --- a/R/check_retracted.R +++ b/R/check_retracted.R @@ -54,6 +54,7 @@ check_retracted <- function(refs) { # Return results output <- list( + refs=refs, n_retracted = n_retracted, n_total = n_total ) diff --git a/data/latest_update.txt b/data/latest_update.txt new file mode 100644 index 0000000..3d03167 --- /dev/null +++ b/data/latest_update.txt @@ -0,0 +1 @@ +Retraction Watch data last retrieved on 1737644383 \ No newline at end of file diff --git a/inst/extdata/example.ris b/inst/extdata/example.ris new file mode 100644 index 0000000..d14f675 --- /dev/null +++ b/inst/extdata/example.ris @@ -0,0 +1,5299 @@ +TY - JOUR +AU - Yan, XD +AU - Liu, JF +AU - Luo, ZP +AU - Ding, QX +AU - Mao, XG +AU - Yan, M +AU - Yang, SG +AU - Hu, XY +AU - Huang, JH +AU - Luo, ZJ +TI - Proteomic profiling of proteins in rat spinal cord induced by contusion injury +T2 - NEUROCHEMISTRY INTERNATIONAL +LA - English +KW - Spinal cord +KW - Contusion +KW - Proteomics +KW - Dynamic change +KW - Rat +KW - Nervous system +KW - GENE-EXPRESSION +KW - MESSENGER-RNA +KW - CELLS +KW - INVOLVEMENT +KW - GALECTIN-3 +KW - BRAIN +KW - HEAT-SHOCK-PROTEIN-70 +KW - ELECTROPHORESIS +KW - OVEREXPRESSION +KW - DEHYDROGENASE +AB - It is widely accepted that mechanical injury to spinal cord can cause nervous system dysfunction, which leads to the loss of movement and sensation. However, the exact molecular mechanism is currently unclear. In this study, contused rat spinal cords were collected at 8 h, 1 day, 3, and 5 days after injury and the expression patterns of the proteins were monitored and quantified with two-dimensional gel electrophoresis-based proteomics. Fifty-one protein spots showed significant regulation at least at one time point. Of the 39 proteins, identified by mass spectrometry analysis and clustered into three down-regulation profiles and two up-regulation profiles, eight contusion-related proteins have been reported in previous proteomic studies of spinal cord whereas 31 proteins were described for the first time. For example, apoptosis-related protein of heat shock 70 kDa protein 1B increased after contusion, reaching the peak at 1 day; septin 7, a protein involved in cytoskeleton organization, maintained a steady increase for the first 5 days after injury; metabolism-related protein of 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 was constantly down-regulated during the whole time course observed; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide, associated with cell cycle progression, showed a gradual increase after contusion. To our knowledge, this is the first case of detailed and dynamic proteomic snapshots of contusion-induced spinal cord injury. Most of the identified proteins were found for the first time to be differentially expressed after spinal cord contusion, which may help explore the complex molecular cascades underlying the progressive pathologic changes in the contused spinal cord. (C) 2010 Elsevier Ltd. All rights reserved. +AD - Fourth Mil Med Univ, Inst Orthopaed, Xijing Hosp, Xian 710032, Peoples R China AD - Fourth Mil Med Univ, Dept Neurol, Xijing Hosp, Xian 710032, Peoples R China AD - 309th Hosp Chinese PLA, Dept Orthopaed, Beijing 100091, Peoples R China AD - Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90050 USA AD - Fourth Mil Med Univ, Dept Neurosurg, Xijing Hosp, Xian 710032, Peoples R China AD - Inst Basic Med Sci, Dept Neurobiol, State Key Lab Prote, Beijing 100850, Peoples R China C3 - Air Force Military Medical University C3 - Air Force Military Medical University C3 - University of California System C3 - University of California Los Angeles C3 - Air Force Military Medical University FU - National Natural Science Foundation of China [30572165] +FX - This work was supported by the National Natural Science Foundation of China (No. 30572165). The authors thank Prof. Shaojun Liu and Dr. Tao Liu (State Key Laboratory of Proteomics. Department of Neurobiology, Institute of Basic Medical Sciences, Beijing) for the valuable technical advice. We are grateful for the excellent technical assistance of technician Lifeng Lan. +PU - PERGAMON-ELSEVIER SCIENCE LTD +PI - OXFORD +PA - THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND +SN - 0197-0186 +SN - 1872-9754 +J9 - NEUROCHEM INT +JI - Neurochem. Int. +DA - JUL +PY - 2010 +VL - 56 +IS - 8 +SP - 971 +EP - 983 +DO - 10.1016/j.neuint.2010.04.007 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000279164900014 +N1 - Times Cited in Web of Science Core Collection: 29 +Total Times Cited: 30 +Cited Reference Count: 52 +ER - + +TY - JOUR +AU - Yan, XD +AU - Liu, T +AU - Yang, SG +AU - Ding, QX +AU - Liu, Y +AU - Zhang, XJ +AU - Que, HP +AU - Wei, KH +AU - Luo, ZJ +AU - Liu, SJ +TI - Proteomic Profiling of the Insoluble Pellets of the Transected Rat Spinal Cord +T2 - JOURNAL OF NEUROTRAUMA +LA - English +KW - precipitated fraction +KW - proteomics +KW - rat +KW - spinal cord +KW - transection +KW - OXIDATIVE STRESS +KW - INDUCED APOPTOSIS +KW - BINDING PROTEIN +KW - EXPRESSION +KW - KINASE +KW - INJURY +KW - MEMBRANE +KW - CELLS +KW - DIFFERENTIATION +KW - DEHYDROGENASE +AB - This study investigated the proteomic changes at different time points in the precipitated pellets of rat spinal cords after applying complete spinal cord transection. By two-dimensional electrophoresis, matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry, MALDI-TOF/TOF and peptide mass fingerprinting analysis, 44 proteins were identified, most of which are membrane and/or organellar proteins. They are mainly involved in metabolic processes (75%), developmental processes (30%), or responses to stimuli (30%), playing negative or positive roles. In particular, decreases of pyruvate dehydrogenase beta, aconitase 2, fumarate hydratase 1, and ATP synthase subunit 6 can lead to ATP depletion by crippling tricarboxylic acid cycle and oxidative phosphorylation. Decreases of several antioxidant proteins such as catalase, peroxiredoxin 1, Parkinson disease 7, and stress-induced phosphoprotein 1 can contribute to the secondary injury of spinal cord. Decreases of development-related 3-phosphoglycerate dehydrogenase and stathmin 1 may be not propitious for spinal cord regeneration. On the other hand, increases of isocitrate dehydrogenase 3 alpha/gamma and glutamate dehydrogenase 1 can help compensate the impaired energy metabolism. Increases of sirtuin 2, crystallin alpha B (CRYAB), and heat shock 27-kDa protein 1 can help resist stresses induced by injury. Increases of adenylate cyclase-associated protein 1 and galactose binding lectin 3 can help regeneration by replaying their roles in neural development. To our knowledge, this is the first case of characterization of the proteomic changes seen in the precipitated fraction of injured spinal cord. Most of the identified proteins were found for the first time to be differentially expressed after spinal cord injury, which may provide new clues about the molecular mechanisms of spinal cord injury and repair. +AD - Inst Basic Med Sci, Dept Neurobiol, State Key Lab Prote, Beijing 100850, Peoples R China AD - Fourth Mil Med Univ, Xijing Hosp, Dept Orthopaed Surg, Xian 710032, Peoples R China AD - Natl Ctr Biomed Anal, Beijing, Peoples R China C3 - Air Force Military Medical University FU - The Chinese National Key Project of Basic Research [001CB510206]; Chinese National Natural Science Foundation [30430310] +FX - This work was supported by The Chinese National Key Project of Basic Research (001CB510206), and the Chinese National Natural Science Foundation (30430310). +PU - MARY ANN LIEBERT, INC +PI - NEW ROCHELLE +PA - 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA +SN - 0897-7151 +SN - 1557-9042 +J9 - J NEUROTRAUM +JI - J. Neurotrauma +DA - FEB +PY - 2009 +VL - 26 +IS - 2 +SP - 179 +EP - 193 +DO - 10.1089/NEU.2008.0533 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000263585100002 +N1 - Times Cited in Web of Science Core Collection: 13 +Total Times Cited: 17 +Cited Reference Count: 39 +ER - + +TY - JOUR +AU - Lu, AP +AU - Wisniewski, JR +AU - Mann, M +TI - Comparative Proteomic Profiling of Membrane Proteins in Rat Cerebellum, Spinal Cord, and Sciatic Nerve +T2 - JOURNAL OF PROTEOME RESEARCH +LA - English +KW - proteomics +KW - neurotransmitter receptor +KW - ion channels +KW - cerebellum +KW - spinal cord +KW - sciatic nerve +KW - MASS-SPECTROMETRY DATA +KW - CODED AFFINITY TAGS +KW - PEPTIDE IDENTIFICATION +KW - MOUSE-BRAIN +KW - QUANTIFICATION +KW - TRANSPORT +KW - ACCURACY +KW - GENOMICS +KW - SAMPLES +KW - HYSTAG +AB - Proteomics is an increasingly powerful technology that can provide in-depth insights into entire proteomes and their variation upon disease. Large-scale proteomics today enables identification and measurement of changes of thousands of proteins from minute amount of tissues. Here, we provide a proteomic profile of three distinct parts of the murine nerve system: cerebellum, spinal cord, and sciatic nerve. We focus on membrane proteins as the key regulators of neural transmission and memory. Rat tissues were homogenized and extracted to remove nonmembrane proteins and the resulting membranes were solubilized with detergents. Proteins were fractionated by size exclusion chromatography, depleted for detergents, digested and analyzed by LC-MS/MS using the LTQ-Orbitrap instrument. With the application of stringent identification criteria, in total, 4124 proteins were identified. Of these proteins, 3528, 3290, and 1649 were mapped to cerebellum, spinal cord, and sciatic nerve, respectively, allowing in-depth mapping of neurotransmitter receptors, ion channels, and transporter proteins. This work is the most in-depth proteomic analysis of nerve tissues to date and provides the first unbiased insights into the proteomes of anatomically and functionally distinct parts of the membrane proteome of the central and peripheral nerve systems. The methods applied here can be directly applied to studying nerve systems and their disorders. +AD - Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany C3 - Max Planck Society PU - AMER CHEMICAL SOC +PI - WASHINGTON +PA - 1155 16TH ST, NW, WASHINGTON, DC 20036 USA +SN - 1535-3893 +SN - 1535-3907 +J9 - J PROTEOME RES +JI - J. Proteome Res. +DA - MAY +PY - 2009 +VL - 8 +IS - 5 +SP - 2418 +EP - 2425 +DO - 10.1021/pr8010364 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000265745300028 +N1 - Times Cited in Web of Science Core Collection: 39 +Total Times Cited: 41 +Cited Reference Count: 34 +ER - + +TY - JOUR +AU - Wang, XL +AU - Shen, JH +AU - Xu, CY +AU - Wan, C +AU - Yang, HY +AU - Qiu, Y +AU - Xu, MM +AU - Duo, W +AU - Sun, TJ +AU - Cui, J +AU - Chu, L +AU - Yang, XD +TI - Proteomic profile of Trichinella spiralis infected mice with acute spinal cord injury: A 4D label-free quantitative analysis +T2 - COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES +LA - English +KW - Spinal cord injury +KW - Helminth therapy +KW - Trichinella spiralis +KW - 4D label-free quantitative proteomics +KW - HYDROGEN-SULFIDE +KW - APOPTOSIS +AB - Spinal cord injury (SCI) can cause severe loss of locomotor and sensory activities, with no ideal treatment. Emerging reports suggest that the helminth therapy is highly effective in relieving numerous inflammatory diseases. Proteomic profiling is often used to elucidate the underlying mechanism behind SCI. Herein, we sys-tematically compared the protein expression profiles of murine SCI spinal cord and Trichinella spiralis treated murine SCI spinal cord, using a 4D label-free technique known for its elevated sensitivity. Relative to the SCI mice, the T. spiralis-treated mice exhibited marked alterations in 91 proteins (31 up-and 60 down-regulated). Based on our Gene Ontology (GO) functional analysis, the differentially expressed proteins (DEPs) were pri-marily enriched in the processes of metabolism, biological regulation, cellular process, antioxidant activity, and other cell functions. In addition, according to the Clusters of Orthologous Groups of protein/EuKaryotic Orthologous Groups (COG/KOG) functional stratification, proteins involved in signaling transduction mecha-nisms belonged to the largest category. Over-expressed DEPs were also enriched in the "NADPH oxidase com-plex", "superoxide anion generation", "other types of O-glycan biosynthesis", and "HIF-1 signaling pathway". Furthermore, the protein-protein interaction (PPI) network identified the leading 10 hub proteins. In conclusion, we highlighted the dynamic proteomic profiling of T. spiralis-treated SCI mice. Our findings provide significant insight into the molecular mechanism behind T. spiralis regulation of SCI. +AD - Bengbu Med Coll, Dept Microbiol & Parasitol, Bengbu, Peoples R China AD - Bengbu Med Coll, Anhui Key Lab Infect & Immunol, Bengbu, Peoples R China AD - Bengbu Med Coll, Affiliated Hosp 2, Bengbu, Peoples R China C3 - Bengbu Medical University C3 - Bengbu Medical University C3 - Bengbu Medical University FU - Program of Natural Science Foundation of the Anhui Higher Education Institutions [KJ2020A0566, KJ20210687]; 512 Talents Development Project of Bengbu Medical College [by51201205, by51201306]; Postgraduate Scientific Research Innovation Program of Bengbu Medical College [Byycx22009]; National University Students' Innovation and Entrepreneurship Training Program [S202010367108, S202110367084]; Science Foundation of Bengbu Medical College [2020bypd007]; Science Foundation of Anhui Province [2008085MH260]; Key Research Platform Open Project of Anhui Province [KLICD-2022-Z1] +FX - This work was supported by the Program of Natural Science Foundation of the Anhui Higher Education Institutions (KJ2020A0566 and KJ20210687); 512 Talents Development Project of Bengbu Medical College (by51201205 and by51201306); the Postgraduate Scientific Research Innovation Program of Bengbu Medical College (Byycx22009); the National University Students' Innovation and Entrepreneurship Training Program (S202010367108 and S202110367084); the Science Foundation of Bengbu Medical College (2020bypd007); the Science Foundation of Anhui Province (2008085MH260) and the Key Research Platform Open Project of Anhui Province (KLICD-2022-Z1). +PU - ELSEVIER SCI LTD +PI - London +PA - 125 London Wall, London, ENGLAND +SN - 0147-9571 +SN - 1878-1667 +J9 - COMP IMMUNOL MICROB +JI - Comp. Immunol. Microbiol. Infect. Dis. +DA - JUN +PY - 2023 +VL - 97 +C7 - 101994 +DO - 10.1016/j.cimid.2023.101994 +C6 - MAY 2023 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001041425500001 +N1 - Times Cited in Web of Science Core Collection: 0 +Total Times Cited: 0 +Cited Reference Count: 44 +ER - + +TY - JOUR +AU - Tilley, DM +AU - Lietz, CB +AU - Cedeno, DL +AU - Kelley, CA +AU - Li, LJ +AU - Vallejo, R +TI - Proteomic Modulation in the Dorsal Spinal Cord Following Spinal Cord Stimulation Therapy in anIn VivoNeuropathic Pain Model +T2 - NEUROMODULATION +LA - English +KW - Low-frequency electrical stimulation +KW - neuropathic pain +KW - protein expression +KW - proteomics +KW - spared nerve injury model +KW - spinal cord stimulation +KW - tandem mass spectrometry +KW - NEUROPATHIC PAIN +KW - EXTRACELLULAR-MATRIX +KW - CEREBROSPINAL-FLUID +KW - NERVE INJURY +KW - ACTIVATION +KW - CYTOKINES +KW - GLIA +KW - INDUCTION +KW - MICROGLIA +AB - Objectives Spinal cord stimulation (SCS) provides relief for patients suffering from chronic neuropathic pain although its mechanism may not be as dependent on electrical interference as classically considered. Recent evidence has been growing regarding molecular changes that are induced by SCS as being a key player in reversing the pain process. Here, we observed the effect of SCS on altering protein expression in spinal cord tissue using a proteomic analysis approach. Methods A microlead was epidurally implanted following induction of an animal neuropathic pain model. After the model was established, stimulation was applied for 72 hours continuously followed by tissue collection and proteomic analysis via tandem mass spectroscopy. Identified proteins were run through online data bases for protein identification and classification of biological processes. Results A significant improvement in mechanical sensitivity was observed following 48 hours of SCS therapy. Proteomic analysis identified 5840 proteins, of which 155 were significantly affected by SCS. Gene ontology data bases indicated that a significant number of proteins were associated to stress response, oxidation/reduction, or extracellular matrix pathways. Additionally, many of the proteins identified also play a role in neuron-glial interactions and are involved in nociception. Conclusions The development of an injury unbalances the proteome of the local neural tissue, neurons, and glial cells, and shifts the proteomic profile to a pain producing state. This study demonstrates the reversal of the injury-induced proteomic state by applying conventional SCS therapy. Additional studies looking at variations in electrical parameters are needed to optimize SCS. +AD - Lumbrera LLC, 8 Berlang Rd, Londonderry, NH 03053 USA AD - Celgene Corp, San Diego, CA USA AD - Stimgen LLC, Bloomington, IL USA AD - Univ Wisconsin Madison, Madison, WI USA AD - Natl Spine & Pain Ctr, Bloomington, IL USA C3 - Bristol-Myers Squibb C3 - Celgene Corporation C3 - University of Wisconsin System C3 - University of Wisconsin Madison FU - Millennium Pain Center, Bloomington, IL, USA +FX - This study was funded by the Millennium Pain Center, Bloomington, IL, USA. +PU - ELSEVIER +PI - AMSTERDAM +PA - RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS +SN - 1094-7159 +SN - 1525-1403 +J9 - NEUROMODULATION +JI - Neuromodulation +DA - JAN +PY - 2021 +VL - 24 +IS - 1 +SP - 22 +EP - 32 +DO - 10.1111/ner.13103 +C6 - MAR 2020 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000562304500001 +N1 - Times Cited in Web of Science Core Collection: 15 +Total Times Cited: 17 +Cited Reference Count: 40 +ER - + +TY - JOUR +AU - Eiró, LG +AU - Ferreira, MKM +AU - Bittencourt, LO +AU - Aragao, WAB +AU - de Souza, MPC +AU - Silva, MCF +AU - Dionizio, A +AU - Buzalaf, MAR +AU - Crespo-López, ME +AU - Lima, RR +TI - Chronic methylmercury exposure causes spinal cord impairment: Proteomic modulation and oxidative stress +T2 - FOOD AND CHEMICAL TOXICOLOGY +LA - English +KW - Mercury +KW - Central nervous system +KW - Protein +KW - oxidative stress +KW - Proteomics +KW - Spinal cord +KW - TOXICOLOGICAL ANALYSIS +KW - INDUCED NEUROTOXICITY +KW - MOLECULAR CHAPERONES +KW - LIPID-PEROXIDATION +KW - INORGANIC MERCURY +KW - RATS +KW - MITOCHONDRIA +KW - INTOXICATION +KW - CYTOSCAPE +KW - PRODUCTS +AB - Methylmercury (MeHg) is considered by the World Health Organization (WHO) as one of the chemicals of greatest public health concern. Although central nervous system (CNS) is the main target organ, the effects over the spinal cord are not well understood, especially in chronic exposure at similar doses to those faced by humans. This study aimed to investigate possible changes on global proteomic profile and oxidative biochemistry status of rats spinal cord, related to the maintenance and balance of the organism functioning, mimicking a human daily exposure by diet (chronic and with relatively low levels). For this, 28 adults male Wistar rats were divided into two groups: MeHg group, which was intoxicated by intragastric gavage with MeHg at a dose of 0.04 mg/kg/day for 60 days, and control group, that received only vehicle. After the exposure period, the spinal cords were collected for evaluation of total mercury levels, proteomic profile, with further bioinformatic overrepresentation analysis (ORA), and oxidative biochemistry, by analyzing the antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (LPO), nitrite levels, measurement of Trolox Equivalent Antioxidant Capacity (TEAC) and Reduced Glutathione (GSH). The MeHg exposure increased total mercury levels in spinal cord parenchyma, which increased lipid peroxidation and nitrite levels , and reduced antioxidant status. The proteomic analysis showed several proteins related to biological processes, cellular components and molecular functions. Moreover, according to the ORA analysis, the proteins are involved in processes such as mitochondrial activity, stress response, cytoskeleton and apoptosis. Therefore, we concluded that exposure to low doses of MeHg can activate the oxidative stress pathway and thus, modulate the status of regulation of several important proteins. +AD - Fed Univ Para, Inst Biol Sci, Lab Funct & Struct Biol, 01 Augusto Correa St, BR-66075 Belem, Para, Brazil AD - Evandro Chagas Inst, Sect Parasitol, Ananindeua, Brazil AD - Fed Univ Para, Lab Mol Pharmacol, BR-66075110 Belem, Para, Brazil AD - Univ Sao Paulo, Bauru Dent Sch, Dept Biol Sci, Bauru, SP, Brazil C3 - Universidade Federal do Para C3 - Instituto Evandro Chagas C3 - Universidade Federal do Para C3 - Universidade de Sao Paulo FU - CNPq; CAPES +FX - We are grateful to CNPq and CAPES for all the fellowship and also to Pro-reitoria de Pesquisa e Pos-graduacao (UFPA) from UFPA (PROPESP, UFPA, Brazil). +PU - PERGAMON-ELSEVIER SCIENCE LTD +PI - OXFORD +PA - THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND +SN - 0278-6915 +SN - 1873-6351 +J9 - FOOD CHEM TOXICOL +JI - Food Chem. Toxicol. +DA - DEC +PY - 2020 +VL - 146 +C7 - 111772 +DO - 10.1016/j.fct.2020.111772 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000604138100004 +N1 - Times Cited in Web of Science Core Collection: 10 +Total Times Cited: 10 +Cited Reference Count: 79 +ER - + +TY - JOUR +AU - Zhang, XJ +AU - Leung, FP +AU - Hsiao, WWL +AU - Tan, S +AU - Li, S +AU - Xu, HX +AU - Sung, JJY +AU - Bian, ZX +TI - Proteome profiling of spinal cord and dorsal root ganglia in rats with trinitrobenzene sulfonic acid-induced colitis +T2 - WORLD JOURNAL OF GASTROENTEROLOGY +LA - English +KW - Inflammatory bowel disease +KW - Trinitrobenzene sulfonic acid +KW - Two-dimensional electrophoresis-based proteomic technique +KW - Dorsal root ganglia +KW - Spinal cord +KW - INFLAMMATORY-BOWEL-DISEASE +KW - HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEINS +KW - INTESTINAL INFLAMMATION +KW - ULCERATIVE-COLITIS +KW - COLONIC INFLAMMATION +KW - RHEUMATOID-ARTHRITIS +KW - MASS-SPECTROMETRY +KW - CREATINE-KINASE +KW - GENE-EXPRESSION +KW - CYCLOPHILIN-A +AB - AIM: To investigate proteomic changes in spinal cord and dorsal root ganglia (DRG) of rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. + METHODS: The colonic myeloperoxidase (MPO) activity and tumor necrosis factor-alpha (TNF-alpha) level were determined. A two-dimensional electrophoresis (2-DE)-based proteomic technique was used to profile the global protein expression changes in the DRG and spinal cord of the rats with acute colitis induced by intracolonic injection of TNBS. + RESULTS: TNBS group showed significantly elevated colonic MPO activity and increased TNF-alpha level. The proteins derived from lumbosacral enlargement of the spinal cord and DRG were resolved by 2-DE; and 26 and 19 proteins that displayed significantly different expression levels in the DRG and spinal cord were identified respectively. Altered proteins were found to be involved in a number of biological functions, such as inflammation/immunity, cell signaling, redox regulation, sulfate transport and cellular metabolism. The overexpression of the protein similar to potassium channel tetramerisation domain containing protein 12 (Kctd 12) and low expression of proteasome subunit alpha type-1 (psma) were validated by Western blotting analysis. + CONCLUSION: TNBS-induced colitis has a profound impact on protein profiling in the nervous system. This result helps understand the neurological pathogenesis of inflammatory bowel disease. (C) 2012 Baishideng. All rights reserved. +AD - Hong Kong Baptist Univ, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China AD - Tsinghua Univ, Minist Educ, Key Lab Bioinformat, Beijing 100084, Peoples R China AD - Tsinghua Univ, Bioinformat Div, TNLIST, Dept Automat, Beijing 100084, Peoples R China AD - Shanghai Univ Tradit Chinese Med, Shanghai 200032, Peoples R China AD - Chinese Univ Hong Kong, Fac Med, Hong Kong, Hong Kong, Peoples R China C3 - Hong Kong Baptist University C3 - Tsinghua University C3 - Tsinghua University C3 - Shanghai University of Traditional Chinese Medicine C3 - Chinese University of Hong Kong FU - Research Grants Council of Hong Kong [RGC-HKBU2/07C]; Hong Kong Jockey Club Institute of Chinese Medicine [JCICM4-07] +FX - The Research Grants Council of Hong Kong, RGC-HKBU2/07C; and The Hong Kong Jockey Club Institute of Chinese Medicine, JCICM4-07 +PU - BAISHIDENG PUBL GRP CO LTD +PI - BEIJING +PA - RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA +SN - 1007-9327 +J9 - WORLD J GASTROENTERO +JI - World J. Gastroenterol. +DA - JUN 21 +PY - 2012 +VL - 18 +IS - 23 +SP - 2914 +EP - 2928 +DO - 10.3748/wjg.v18.i23.2914 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000309210900005 +N1 - Times Cited in Web of Science Core Collection: 6 +Total Times Cited: 9 +Cited Reference Count: 74 +ER - + +TY - JOUR +AU - Kang, SK +AU - So, HH +AU - Moon, YS +AU - Kim, CH +TI - Proteomic analysis of injured spinal cord tissue proteins using 2-DE and MALDI-TOF MS +T2 - PROTEOMICS +LA - English +KW - mass spectrophotometry +KW - neural function +KW - spinal cord injury +KW - two dimensional electrophoresis +KW - ADULT-RAT +KW - PROMOTES RECOVERY +KW - GROWTH-FACTOR +KW - IN-VIVO +KW - PROLIFERATION +KW - EXPRESSION +KW - CELLS +KW - METHYLPREDNISOLONE +KW - VACCINATION +KW - SIGNAL +AB - Spinal cord injury (SCI) induces a progressive pathophysiology affecting cell survival and neurological integrity via complex and evolving molecular cascades whose interrelationships are not fully understood. Acute injury to the spinal cord undergoes sequential pathological change including hemorrhage, edema, axonal and neuronal necrosis, and demyelination. In the present study, we aimed to establish the proteomic profiles and characterization of the total protein expressed in traumatic injured spinal cord tissue by using 2-DE and matrix assisted laser desorption/ionization-TOF MS (MALDI-TOF MS). We performed proteomic analysis using 2-DE and MS to describe total proteins and differential proteins expression between normal and traumatic injured spinal cord tissues. The study discovered 947 total proteins and analyzed 219 and 270 proteins from normal and injured tissue, respectively. After 24 h of traumatic damage induction, the injured spinal cord tissue up-regulated over 39 proteins including neurofilament light chain, annexin 5, heat shock protein, tubulin beta, peripherin, glial fibrillary acidic protein delta, peroxiredoxin 2, and apolipoprotein A. Twenty-one proteins showed reduction. The majority of the modulated proteins belonged to the 13 functional categories. Proteins that were identified with neural functional category in injured tissue were considered most likely to be involved in wound healing response coupled with neurogenesis and gliogenesis. +AD - Pusan Natl Univ, Coll Med, Dept Physiol, Pusan 609735, South Korea AD - Pusan Natl Univ, Coll Med, Dept Anesthesiol, Pusan 609735, South Korea C3 - Pusan National University C3 - Pusan National University PU - WILEY +PI - HOBOKEN +PA - 111 RIVER ST, HOBOKEN 07030-5774, NJ USA +SN - 1615-9853 +SN - 1615-9861 +J9 - PROTEOMICS +JI - Proteomics +DA - MAY +PY - 2006 +VL - 6 +IS - 9 +SP - 2797 +EP - 2812 +DO - 10.1002/pmic.200500621 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000237773500014 +N1 - Times Cited in Web of Science Core Collection: 53 +Total Times Cited: 61 +Cited Reference Count: 30 +ER - + +TY - JOUR +AU - Harada, S +AU - Matsuura, W +AU - Takano, M +AU - Tokuyama, S +TI - RETRACTED: Proteomic Profiling in the Spinal Cord and Sciatic Nerve in a Global Cerebral Ischemia-Induced Mechanical Allodynia Mouse Model (Retracted article. See vol. 42, pg. 1957, 2019) +T2 - BIOLOGICAL & PHARMACEUTICAL BULLETIN +LA - English +KW - global ischemia +KW - pain +KW - spinal cord +KW - sciatic nerve +KW - proteome +KW - CENTRAL POSTSTROKE PAIN +KW - KERATAN SULFATE PROTEOGLYCAN +KW - MYOSIN-II +KW - CREATINE-KINASE +KW - GROWTH-FACTOR +KW - NEURITE OUTGROWTH +KW - NEUROPATHIC PAIN +KW - EXPRESSION +KW - IDENTIFICATION +KW - REGULATOR +AB - Central post-stroke pain (CPSP) is one of the complications of cerebral ischemia and neuropathic pain syndrome. At present, there are few studies of pain in regions such as the spinal cord or sciatic nerve in cerebral ischemic animal models. To identify proteomic changes in the spinal cord and sciatic nerve in global cerebral ischemic model mice, in the present study we performed an investigation using proteomic methods. In a comparison between the intensity of protein spots obtained from a sham and that from a bilateral carotid artery occulusion (BCAO) in spinal cord and sciatic nerve, the levels of 10 (spinal cord) and 7 (sciatic nerve) protein spots were altered. The protein levels in the spinal cord were significantly increased in N-G,N-G-dimethylarginine dimethylaminohydrolase 1 (DDAH1), 6-phosphogluconolactonase isoform 1, and precursor apoprotein A-I and decreased in dihydropyrimidinase-related protein 2 (CRMP-2), enolase 1B, rab guano sine 5'-diphosphate (GDP) dissociation inhibitor beta, septin-2 isoform a, isocitrate dehydrogenase subunit alpha, cytosolic malate dehydrogenase, and adenosine triphosphate synthase. The protein levels in the sciatic nerve were significantly increased in a mimecan precursor, myosin light chain 1/3, and myosin regulatory light chain 2 (MLC2), and decreased in dihydropyrimidinase-related protein 3 (CRMP-4), protein disulfide-isomerase A3, 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1, and B-type creatine kinase. In addition, CRMP-2 and CRMP-4 protein levels were decreased, and DDAH1 and MLC2 protein levels were increased on day 1 after BCAO using Western blotting. These results suggested that changes in these proteins may be involved in the regulation of CPSP. +AD - Kobe Gakuin Univ, Sch Pharmaceut Sci, Dept Clin Pharm, Chuo Ku, 1-1-3 Minatojima, Kobe, Hyogo 6508586, Japan AD - Kobe Gakuin Univ, Sch Pharmaceut Sci, Dept Life Sci Pharm, Chuo Ku, 1-1-3 Minatojima, Kobe, Hyogo 6508586, Japan C3 - Kobe Gakuin University C3 - Kobe Gakuin University FU - Ministry of Education, Culture, Sports, Science and Technology of Japan [25462458]; Grants-in-Aid for Scientific Research [15K16533, 25462458] Funding Source: KAKEN +FX - This study was supported by Grants in-Aid and by Special Coordination Funds from Grants-in-Aid for Scientific Research (C) (25462458) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. +PU - PHARMACEUTICAL SOC JAPAN +PI - TOKYO +PA - 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN +SN - 0918-6158 +J9 - BIOL PHARM BULL +JI - Biol. Pharm. Bull. +DA - FEB +PY - 2016 +VL - 39 +IS - 2 +SP - 230 +EP - 238 +DO - 10.1248/bpb.b15-00647 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000369124500011 +N1 - Times Cited in Web of Science Core Collection: 12 +Total Times Cited: 14 +Cited Reference Count: 80 +ER - + +TY - JOUR +AU - Engelen-Lee, J +AU - Blokhuis, AM +AU - Spliet, WGM +AU - Pasterkamp, RJ +AU - Aronica, E +AU - Demmers, JAA +AU - Broekhuizen, R +AU - Nardo, G +AU - Bovenschen, N +AU - Van Den Berg, LH +TI - Proteomic profiling of the spinal cord in ALS: decreased ATP5D levels suggest synaptic dysfunction in ALS pathogenesis +T2 - AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION +LA - English +KW - Amyotrophic lateral sclerosis +KW - Two-Dimensional Differential Gel Electrophoresis (2D-DIGE) +KW - spinal cord +KW - proteomics +KW - ATP5D +KW - synaptic mitochondrial defect +KW - AMYOTROPHIC-LATERAL-SCLEROSIS +KW - MOTOR-NEURON INJURY +KW - CEREBROSPINAL-FLUID +KW - MASS-SPECTROMETRY +KW - DELTA-SUBUNIT +KW - PATHWAYS +KW - BIOMARKERS +KW - PROTEINS +KW - MOUSE +KW - DEGENERATION +AB - Background: We aimed to gain new insights into the pathogenesis of sporadic ALS (sALS) through a comprehensive proteomic analysis. Methods: Protein profiles of the anterior and posterior horn in post-mortem spinal cord samples of 10 ALS patients and 10 controls were analysed using 2D-differential gel electrophoresis. The identified protein spots with statistically significant level changes and a spot ratio >2.0 were analysed by LC-MS/MS. Results: In the posterior horn only 3 proteins were differentially expressed. In the anterior horn, 16 proteins with increased levels and 2 proteins with decreased levels were identified in ALS compared to controls. The identified proteins were involved in mitochondrial metabolism, calcium homeostasis, protein metabolism, glutathione homeostasis, protein transport and snRNP assembly. The two proteins with decreased levels, ATP5D and calmodulin, were validated by Western blot and immunostaining. Immunohistochemical and immunofluorescent double staining of ATP5D and synaptophysin showed that the reduction of ATP5D was most pronounced at synapses. Conclusions: We speculate that mitochondrial dysfunction in synaptic clefts could play an important role in sALS pathogenesis. A similar approach revealed decreased calmodulin expression mainly in the neuronal body and dendrites of ALS patients. These findings contribute to a deeper understanding of the disease process underlying ALS. +AD - Acad Med Ctr, Dept Neurol, Amsterdam, Netherlands AD - Univ Med Ctr Utrecht, Dept Translat Neurosci, Brain Ctr Rudolf Magnus, Utrecht, Netherlands AD - Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands AD - Acad Med Ctr, Dept Neuro Pathol, Amsterdam, Netherlands AD - Erasmus Univ, Prote Ctr, Med Ctr, Rotterdam, Netherlands AD - Mario Negri Inst Pharmacol Res, Dept Mol Biochem & Pharmacol, Milan, Italy AD - Univ Med Ctr Utrecht, Lab Translat Immunol, Utrecht, Netherlands AD - Univ Med Ctr Utrecht, Dept Neurol & Neurosurg, Brain Ctr Rudolf Magnus, Utrecht, Netherlands C3 - University of Amsterdam C3 - Academic Medical Center Amsterdam C3 - Utrecht University C3 - Utrecht University Medical Center C3 - Utrecht University C3 - Utrecht University Medical Center C3 - University of Amsterdam C3 - Academic Medical Center Amsterdam C3 - Erasmus University Rotterdam C3 - Erasmus MC C3 - Istituto di Ricerche Farmacologiche Mario Negri IRCCS C3 - Utrecht University C3 - Utrecht University Medical Center C3 - Utrecht University C3 - Utrecht University Medical Center FU - Baxter International Inc.; Prinses Beatrix Spierfonds; Netherlands Organisation for Health Research and Development (ZonMW-VICI: L.H.v.d.B); Netherlands ALS Foundation; European Community [259867] +FX - L.H.v.d.B. received an educational grant from Baxter International Inc., and served on a scientific advisory board of Biogen Idec and Cytokinetics. This work was supported by funding from the Prinses Beatrix Spierfonds, the Netherlands Organisation for Health Research and Development (ZonMW-VICI: L.H.v.d.B), the Netherlands ALS Foundation, and The European Community's Health Seventh Framework Programme [grant agreement no. 259867]. +PU - TAYLOR & FRANCIS LTD +PI - ABINGDON +PA - 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND +SN - 2167-8421 +SN - 2167-9223 +J9 - AMYOTROPH LAT SCL FR +JI - Amyotroph. Lateral Scher. Frontotemp. Degenerat. +PY - 2017 +VL - 18 +IS - 3-4 +SP - 210 +EP - 220 +DO - 10.1080/21678421.2016.1245757 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000400792800006 +N1 - Times Cited in Web of Science Core Collection: 32 +Total Times Cited: 36 +Cited Reference Count: 36 +ER - + +TY - JOUR +AU - Baldan-Martin, M +AU - Martin-Rojas, T +AU - Corbacho-Alonso, N +AU - Lopez, JA +AU - Sastre-Oliva, T +AU - Gil-Dones, F +AU - Vazquez, J +AU - Arevalo, JM +AU - Mourino-Alvarez, L +AU - Barderas, MG +TI - Comprehensive Proteomic Profiling of Pressure Ulcers in Patients with Spinal Cord Injury Identifies a Specific Protein Pattern of Pathology +T2 - ADVANCES IN WOUND CARE +LA - English +KW - pressure ulcer +KW - spinal cord injury +KW - proteomics +KW - tandem mass tags +KW - MASS-SPECTROMETRY +KW - PEPTIDE IDENTIFICATION +KW - STEM-CELLS +KW - MATRIX +KW - FIBRONECTIN +KW - COMPLEMENT +KW - GROWTH +KW - PHASE +KW - SKIN +KW - LIPOPROTEINS +AB - Objective: Severe pressure ulcers (PUs) do not respond to conservative wound therapy and need surgical repair. To better understand the pathogenesis and to advance on new therapeutic options, we focused on the proteomic analysis of PU, which offers substantial opportunities to identify significant changes in protein abundance during the course of PU formation in an unbiased manner. Approach: To better define the protein pattern of this pathology, we performed a proteomic approach in which we compare severe PU tissue from spinal cord injury (SCI) patients with control tissue from the same patients. Results: We found 76 proteins with difference in abundance. Of these, 10 proteins were verified as proteins that define the pathology: antithrombin-III, alpha-1-antitrypsin, kininogen-1, alpha-2-macroglobulin, fibronectin, apolipoprotein A-I, collagen alpha-1 (XII) chain, haptoglobin, apolipoprotein B-100, and complement factor B. Innovation: This is the first study to analyze differential abundance protein of PU tissue from SCI patients using high-throughput protein identification and quantification by tandem mass tags followed by liquid chromatography tandem mass spectrometry. Conclusion: Differential abundance proteins are mainly involved in tissue regeneration. These proteins might be considered as future therapeutic options to enhance the physiological response and permit cellular repair of damaged tissue. +AD - Natl Hosp Parapleg HNP, SESCAM, Dept Vasc Physiopathol, Toledo, Spain AD - Natl Hosp Parapleg HNP, SESCAM, Dept Plast Surg, Toledo, Spain AD - CNIC, Cardiovasc Prote Lab, Madrid, Spain AD - CNIC, CIBER CV, Madrid, Spain C3 - Centro Nacional de Investigaciones Cardiovasculares (CNIC) C3 - CIBER - Centro de Investigacion Biomedica en Red C3 - CIBERCV C3 - Centro Nacional de Investigaciones Cardiovasculares (CNIC) FU - Instituto de Salud Carlos III [PI14/01917, PI18/00995, PT13/0001/0013]; ERDF/ESF, "Investing in your future''; Redes Tematicas de Investigacion Cooperativa (FONDOS FEDER) [RD12/0042/0071]; Sociedad Espanola de Cardiologia para la Investigacion Basica 2017; Grant PRB3 [IPT17/0019-ISCIII-SGEFI/ERDF] +FX - This work was supported by grants from the Instituto de Salud Carlos III (PI14/01917, PI18/00995, PT13/0001/0013) for Funding: ISCIII ("PI14/01917, PI18/00995, PT13/0001/0013)'', co-funded by ERDF/ESF, "Investing in your future''. Redes Tematicas de Investigacion Cooperativa (FONDOS FEDER, RD12/0042/0071). Sociedad Espanola de Cardiologia para la Investigacion Basica 2017. Grant PRB3 (IPT17/0019-ISCIII-SGEFI/ERDF). These results are aligned with the Spanish initiative on the Human Proteome Project (SpHPP). +PU - MARY ANN LIEBERT, INC +PI - NEW ROCHELLE +PA - 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA +SN - 2162-1918 +SN - 2162-1934 +J9 - ADV WOUND CARE +JI - Adv. Wound Care +DA - MAY 1 +PY - 2020 +VL - 9 +IS - 5 +SP - 277 +EP - 294 +DO - 10.1089/wound.2019.0968 +C6 - JUN 2019 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000475822900001 +N1 - Times Cited in Web of Science Core Collection: 4 +Total Times Cited: 4 +Cited Reference Count: 75 +ER - + +TY - JOUR +AU - Nelvagal, HR +AU - Hurtado, ML +AU - Eaton, SL +AU - Kline, RA +AU - Lamont, DJ +AU - Sands, MS +AU - Wishart, TM +AU - Cooper, JD +TI - Comparative proteomic profiling reveals mechanisms for early spinal cord vulnerability in CLN1 disease +T2 - SCIENTIFIC REPORTS +LA - English +KW - NEURONAL CEROID-LIPOFUSCINOSIS +KW - DIRECTED GENE-THERAPY +KW - MOUSE MODEL +KW - OXIDATIVE STRESS +KW - MUSCULAR-ATROPHY +KW - BRAIN +KW - PROTEIN +KW - PATHOGENESIS +KW - STORAGE +KW - NEURODEGENERATION +AB - CLN1 disease is a fatal inherited neurodegenerative lysosomal storage disease of early childhood, caused by mutations in the CLN1 gene, which encodes the enzyme Palmitoyl protein thioesterase-1 (PPT-1). We recently found significant spinal pathology in Ppt1-deficient (Ppt1(-/-)) mice and human CLN1 disease that contributes to clinical outcome and precedes the onset of brain pathology. Here, we quantified this spinal pathology at 3 and 7 months of age revealing significant and progressive glial activation and vulnerability of spinal interneurons. Tandem mass tagged proteomic analysis of the spinal cord of Ppt1(-/-)and control mice at these timepoints revealed a significant neuroimmune response and changes in mitochondrial function, cell-signalling pathways and developmental processes. Comparing proteomic changes in the spinal cord and cortex at 3 months revealed many similarly affected processes, except the inflammatory response. These proteomic and pathological data from this largely unexplored region of the CNS may help explain the limited success of previous brain-directed therapies. These data also fundamentally change our understanding of the progressive, site-specific nature of CLN1 disease pathogenesis, and highlight the importance of the neuroimmune response. This should greatly impact our approach to the timing and targeting of future therapeutic trials for this and similar disorders. +AD - Washington Univ, Sch Med, Dept Pediat, Div Genet & Genom Med, 660 S Euclid Ave, St Louis, MO 63110 USA AD - Washington Univ, Sch Med, Dept Genet, 660 S Euclid Ave, St Louis, MO 63110 USA AD - Washington Univ, Sch Med, Dept Neurol, 660 S Euclid Ave, St Louis, MO 63110 USA AD - Washington Univ, Sch Med, Dept Med, 660 S Euclid Ave, St Louis, MO 63110 USA AD - Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, London, England AD - Univ Edinburgh, Roslin Inst, Easter Bush, Midlothian, Scotland AD - Univ Edinburgh, Royal Dick Sch Vet Studies, Easter Bush, Midlothian, Scotland AD - Univ Dundee, Coll Life Sci, FingerPrints Prote Facil, Dundee, Scotland C3 - Washington University (WUSTL) C3 - Washington University (WUSTL) C3 - Washington University (WUSTL) C3 - Washington University (WUSTL) C3 - University of London C3 - King's College London C3 - UK Research & Innovation (UKRI) C3 - Biotechnology and Biological Sciences Research Council (BBSRC) C3 - Roslin Institute C3 - University of Edinburgh C3 - University of Edinburgh C3 - University of Dundee FU - NIH NINDS [043205]; King's College London Graduate School International Studentship; BBSRC ISP funding; BBSRC [BBS/E/D/10002071] Funding Source: UKRI +FX - This work was supported by NIH NINDS 043205 to MSS and JDC, and a King's College London Graduate School International Studentship award to HRN. BBSRC ISP funding for SLE and TMW, Euan MacDonald Center for MND Research for RAK. The authors would like to acknowledge Drs. Marion Bonneau and Alison Barnwell for their advice and comments on the manuscript, and Dr. Brian DeBosch and Cassandra Higgins for invaluable assistance with Western blotting. +PU - NATURE PORTFOLIO +PI - BERLIN +PA - HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY +SN - 2045-2322 +J9 - SCI REP-UK +JI - Sci Rep +DA - SEP 16 +PY - 2020 +VL - 10 +IS - 1 +C7 - 15157 +DO - 10.1038/s41598-020-72075-7 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000573763800010 +N1 - Times Cited in Web of Science Core Collection: 9 +Total Times Cited: 10 +Cited Reference Count: 68 +ER - + +TY - JOUR +AU - Corrêa, MG +AU - Bittencourt, LO +AU - Nascimento, PC +AU - Ferreira, RO +AU - Aragao, WAB +AU - Silva, MCF +AU - Gomes-Leal, W +AU - Fernandes, MS +AU - Dionizio, A +AU - Buzalaf, MR +AU - Crespo-Lopez, ME +AU - Lima, RR +TI - Spinal cord neurodegeneration after inorganic mercury long-term exposure in adult rats: Ultrastructural, proteomic and biochemical damages associated with reduced neuronal density +T2 - ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY +LA - English +KW - Mercury +KW - Mercury chloride +KW - Spinal cord +KW - Neurotoxicology +KW - Proteomics +KW - CNS +KW - FIBRILLARY ACIDIC PROTEIN +KW - OXIDATIVE STRESS +KW - MOTOR CORTEX +KW - NITRIC-OXIDE +KW - METHYLMERCURY +KW - TRANSPORT +KW - S100-BETA +KW - ACTIN +KW - INTOXICATION +KW - COMPLEMENT +AB - Mercury chloride (HgCl2) is a chemical pollutant widely found in the environment. This form of mercury is able to promote several damages to the Central Nervous System (CNS), however the effects of HgCl2 on the spinal cord, an important pathway for the communication between the CNS and the periphery, are still poorly understood. The aim of this work was to investigate the effects of HgCl2 exposure on spinal cord of adult rats. For this, animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. Then, they were euthanized, the spinal cord collected and we investigated the mercury concentrations in medullary parenchyma and the effects on oxidative biochemistry, proteomic profile and tissue structures. Our results showed that exposure to this metal promoted increased levels of Hg in the spinal cord, impaired oxidative biochemistry by triggering oxidative stress, mudulated antioxidant system proteins, energy metabolism and myelin structure; as well as caused disruption in the myelin sheath and reduction in neuronal density. Despite the low dose, we conclude that prolonged exposure to HgCl2 triggers biochemical changes and modulates the expression of several proteins, resulting in damage to the myelin sheath and reduced neuronal density in the spinal cord. +AD - Fed Univ Para, Inst Biol Sci, Lab Funct & Struct Biol, Augusto Correa St 1,Campus Guama, BR-66075900 Belem, Para, Brazil AD - Fed Univ Para, Inst Biol Sci, Lab Expt Neuroprotect & Neuroregenerat, Belem, Para, Brazil AD - Univ Sao Paulo, Bauru Dent Sch, Dept Biol Sci, Bauru, SP, Brazil AD - Fed Univ Para, Inst Biol Sci, Lab Mol Pharmacol, Belem, Para, Brazil C3 - Universidade Federal do Para C3 - Universidade Federal do Para C3 - Universidade de Sao Paulo C3 - Universidade Federal do Para FU - Coordenacdo de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) [001]; Brazilian National Council for Scientific and Technological Development (CNPq) +FX - This study was financed in part by the Coordenacdo de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) Finance Code 001. This research was supported by the Brazilian National Council for Scientific and Technological Development (CNPq). +PU - ACADEMIC PRESS INC ELSEVIER SCIENCE +PI - SAN DIEGO +PA - 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA +SN - 0147-6513 +SN - 1090-2414 +J9 - ECOTOX ENVIRON SAFE +JI - Ecotox. Environ. Safe. +DA - MAR 15 +PY - 2020 +VL - 191 +C7 - 110159 +DO - 10.1016/j.ecoenv.2019.110159 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000514011400003 +N1 - Times Cited in Web of Science Core Collection: 26 +Total Times Cited: 26 +Cited Reference Count: 76 +ER - + +TY - JOUR +AU - Guo, Y +AU - Xu, BH +AU - Sun, ZX +AU - Wu, YT +AU - Shi, W +AU - Wang, J +AU - Meng, XB +AU - Ge, W +AU - Wang, GH +TI - Quantitative protein profiling and pathway analysis of spinal arteriovenous malformations +T2 - MICROVASCULAR RESEARCH +LA - English +KW - Spinal arteriovenous malformation +KW - Proteomic +KW - Angiogenesis +KW - Focal adhesion +KW - Ribosome +KW - ENDOTHELIAL GROWTH-FACTOR +KW - FOCAL ADHESION KINASE +KW - MATRIX METALLOPROTEINASES +KW - VASCULAR MALFORMATIONS +KW - CLINICAL-FEATURES +KW - HUMAN BRAIN +KW - ANGIOGENESIS +KW - EXPRESSION +KW - INHIBITORS +KW - OUTCOMES +AB - Spinal arteriovenous malformations (sAVM) are rare and heterogeneous group of blood vessel disorders that affect spinal cord function directly or indirectly; however, the pathogenesis of sAVM is still unclear. In this study, we compared four sAVM specimens obtained during surgery and donated control samples in a Tandem Mass Tag (TMT)-labeled proteomic analysis. We identified 3101 proteins, 654 of which were differentially expressed in sAVM samples compared with the controls. Of these, 96 proteins were upregulated and 358 proteins were downregulated. Gene ontology (GO) analysis revealed that extracellular matrix organization in the biological process category and integrin-binding proteins in the molecular function category were the most enriched items. Two significant differentially expressed proteins (MYLK and MMP9) were verified by Western blot analysis. The pathway analysis indicated that the differentially expressed proteins in the pathways of angiogenesis, focal adhesion and cytoplasmic ribosome contributed to sAVM. The changes in protein profiles identified in this proteomic study provide an improved understanding of the pathogenesis of sAVM. The proteomics data are available via ProteomeXchange with identifier PXD007982. +AD - Tsinghua Univ, Tsinghua Changgung Hosp, Med Ctr, Dept Neurosurg, 168 Litang Rd, Beijing 102218, Peoples R China AD - Chinese Acad Med Sci, Sch Basic Med, Peking Union Med Coll, Inst Basic Med Sci,State Key Lab Med Mol Biol, Beijing 100005, Peoples R China AD - Chinese Acad Med Sci, Sch Basic Med, Peking Union Med Coll, Inst Basic Med Sci,Dept Immunol, Beijing 100005, Peoples R China AD - Shenzhen Ctr Dis Control & Prevent, Inst Toxicol, Key Lab Modern Toxicol Shenzhen, Shenzhen 518055, Peoples R China AD - Tsinghua Univ, Sch Life Sci, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China C3 - Tsinghua University C3 - Chinese Academy of Medical Sciences - Peking Union Medical College C3 - Peking Union Medical College C3 - Chinese Academy of Medical Sciences - Peking Union Medical College C3 - Peking Union Medical College C3 - Institute of Basic Medical Sciences - CAMS C3 - Shenzhen Center for Disease Control & Prevention (SZCDC) C3 - Tsinghua University FU - National Natural Science Foundation of China [81472817]; Beijing Tsinghua Changgung Hospital Fund [12014C7006]; Tsinghua University Initiative Scientific Research Program [2015THZ0]; Neuro-oncology Project from Chinese Anti-Cancer Association [CSNO-2016-MSD05]; Beijing Municipal Science & technology Commission [Z171100001017199]; CAMS Innovation Fund for Medical Sciences [2016-I2M-1-004]; Shanghai Brain-Intelligence Project from STCSM [16JC1420500, 16JC1420502]; National Postdoctoral Program for Innovative Talents [BX201700162] +FX - This work was supported by the National Natural Science Foundation of China [grant number 81472817]; Beijing Tsinghua Changgung Hospital Fund [grant number 12014C7006]; Tsinghua University Initiative Scientific Research Program [grant number 2015THZ0]; Neuro-oncology Project from Chinese Anti-Cancer Association [grant number CSNO-2016-MSD05]; Beijing Municipal Science & technology Commission [grant number Z171100001017199]; the CAMS Innovation Fund for Medical Sciences [grant number 2016-I2M-1-004]; the Shanghai Brain-Intelligence Project from STCSM [grant number 16JC1420500, 16JC1420502]; the National Postdoctoral Program for Innovative Talents [grant number BX201700162]. +PU - ACADEMIC PRESS INC ELSEVIER SCIENCE +PI - SAN DIEGO +PA - 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA +SN - 0026-2862 +SN - 1095-9319 +J9 - MICROVASC RES +JI - Microvasc. Res. +DA - NOV +PY - 2018 +VL - 120 +SP - 47 +EP - 54 +DO - 10.1016/j.mvr.2018.06.002 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000449037600008 +N1 - Times Cited in Web of Science Core Collection: 3 +Total Times Cited: 4 +Cited Reference Count: 33 +ER - + +TY - JOUR +AU - Dreger, M +AU - Mika, J +AU - Bieller, A +AU - Jahnel, R +AU - Gillen, C +AU - Schaefer, MKH +AU - Weihe, E +AU - Hucho, F +TI - Analysis of the dorsal spinal cord synaptic architecture by combined proteome analysis and in situ hybridization +T2 - JOURNAL OF PROTEOME RESEARCH +LA - English +KW - subcellular proteomics +KW - complex membrane structure +KW - MALDI-TOF-MS +KW - in situ hybridization +KW - nociception +KW - pain +KW - dorsal horn +KW - spinal cord +KW - subcellular fractionation +KW - POSTSYNAPTIC DENSITY FRACTION +KW - RIM-BINDING PROTEINS +KW - MEMBRANE-PROTEINS +KW - IDENTIFICATION +KW - BRAIN +KW - FAMILY +KW - LOCALIZATION +KW - CYTOMATRIX +KW - MIXTURES +KW - COMPLEX +AB - The proteomic analysis of tissue samples is an analytical challenge, because identified gene products not only have to be assigned to subcellular structures, but also to cell subpopulations. We here report a strategy of combined subcellular proteomic profiling and in situ hybridization to assign proteins to subcellular sites in subsets of cells within the dorsal region of rat spinal cord. With a focus on synaptic membranes, which represent a complex membrane protein structure composed of multiple integral membrane proteins and networks of accessory structural proteins, we also compared different two-dimensional gel electrophoresis systems for the separation of the proteins. Using MALDI mass spectrometric protein identification based on peptide mass fingerprints, we identified in total 122 different gene products within the different synaptic membrane subfractions. The tissue structure of the dorsal region of the spinal cord is complex, and different layers of neurons can be distinguished neuroanatomically. Proteomic data combined with an in situ hybridization analysis for the detection of mRNA was used to assign selected gene products, namely the optical atrophy protein OPA-1, the presynaptic cytomatrix protein KIAA0378/CAST1, and the uncharacterized coiled-coil-helix-coiled-coil-helix domain containing protein 3 (hypothetical protein FLJ20420), to cell subsets of the dorsal area of the spinal cord. Most striking, KIAA0378/CAST1 mRNA was found only sparsely within the dorsal horn of the spinal cord, but highly abundant within the dorsal root ganglion. This finding, combined with the identification of KlAA0378/CAST1 within the synaptic membrane fraction of the spinal cord at the protein level, are consistent with the reported presynaptic localization of CAST, predominantly within the tissue we investigated primarily attributable to primary afferent sensory neurons. Our approach may be of use in broader studies to characterize the proteomes of neural tissue. +AD - Free Univ Berlin, Inst Chem Biochem, D-1000 Berlin, Germany AD - Univ Marburg, Dept Mol Neurosci, Inst Anat & Cell Biol, Marburg, Germany AD - Grunenthal GmbH, Mol Pharmacol, Aachen, Germany AD - Univ Oxford, Univ Lab Physiol, Oxford OX1 3PT, England AD - Polish Acad Sci, Inst Pharmacol, Dept Mol Neuropharmacol, PL-31343 Krakow, Poland C3 - Free University of Berlin C3 - Philipps University Marburg C3 - Grunenthal Group C3 - University of Oxford C3 - Polish Academy of Sciences PU - AMER CHEMICAL SOC +PI - WASHINGTON +PA - 1155 16TH ST, NW, WASHINGTON, DC 20036 USA +SN - 1535-3893 +SN - 1535-3907 +J9 - J PROTEOME RES +JI - J. Proteome Res. +DA - MAR-APR +PY - 2005 +VL - 4 +IS - 2 +SP - 238 +EP - 249 +DO - 10.1021/pr049870w +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000228421900006 +N1 - Times Cited in Web of Science Core Collection: 7 +Total Times Cited: 7 +Cited Reference Count: 46 +ER - + +TY - JOUR +AU - Herzberg, D +AU - Strobel, P +AU - Müller, H +AU - Meneses, C +AU - Werner, M +AU - Bustamante, H +TI - Proteomic profiling of proteins in the dorsal horn of the spinal cord in dairy cows with chronic lameness +T2 - PLOS ONE +LA - English +KW - ENDOPLASMIC-RETICULUM STRESS +KW - NEUROPATHIC PAIN +KW - HEALTHY CONTROLS +KW - ANIMAL-MODELS +KW - HSP70 +KW - MECHANISMS +KW - RECEPTORS +KW - ENOLASE +KW - ROLES +KW - PEROXIREDOXIN +AB - Chronic lameness affects bovine welfare and has a negative economic impact in dairy industry. Moreover, due to the translational gap between traditional pain models and new drugs development for treating chronic pain states, naturally occurring painful diseases could be a potential translational tool for chronic pain research. We therefore employed liquid chromatography tandem mass spectrometry (LC-MS/MS) to stablish the proteomic profile of the spinal cord samples from lumbar segments (L2-L4) of chronic lame dairy cows. Data were validated and quantified through software tool (Scaffold (R) v 4.0) using output data from two search engines (SEQUEST (R) and X-Tandem (R)). Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis was performed to detect proteins interactions. LC-MS/MS identified a total amount of 177 proteins; of which 129 proteins were able to be quantified. Lame cows showed a strong upregulation of interacting proteins with chaperone and stress functions such as Hsp70 (p < 0.006), Hsc70 (p < 0.0079), Hsp90 (p < 0.015), STIP (p > 0.0018) and Grp78 (p <0.0068), and interacting proteins associated to glycolytic pathway such as; gamma-enolase (p < 0.0095), alpha-enolase (p < 0.013) and hexokinase-1 (p < 0.028). It was not possible to establish a clear network of interaction in several upregulated proteins in lame cows. Non-interacting proteins were mainly associated to redox process and cytoskeletal organization. The most relevant down regulated protein in lame cows was myelin basic protein (MBP) (p < 0.02). Chronic inflammatory lameness in cows is associated to increased expression of stress proteins with chaperone, metabolism, redox and structural functions. A state of endoplasmic reticulum stress and unfolded protein response (UPR) might explain the changes in protein expression in lame cows; however, further studies need to be performed in order to confirm these findings. +AD - Univ Austral Chile, Fac Vet Sci, Vet Clin Sci Dept, Valdivia, Chile AD - Univ Austral Chile, Fac Vet Sci, Anim Sci Dept, Valdivia, Chile AD - North Caroline State Univ, Comparat Biomed Sci Grad Program, Coll Vet Med, Raleigh, NC USA C3 - Universidad Austral de Chile C3 - Universidad Austral de Chile C3 - North Carolina State University FU - Conicyt [21150613] +FX - This work was supported by Conicyt/Scholarship No 21150613. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. +PU - PUBLIC LIBRARY SCIENCE +PI - SAN FRANCISCO +PA - 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA +SN - 1932-6203 +J9 - PLOS ONE +JI - PLoS One +DA - JAN 28 +PY - 2020 +VL - 15 +IS - 1 +C7 - e0228134 +DO - 10.1371/journal.pone.0228134 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000534605400043 +N1 - Times Cited in Web of Science Core Collection: 5 +Total Times Cited: 5 +Cited Reference Count: 95 +ER - + +TY - JOUR +AU - Bastone, A +AU - Fumagalli, E +AU - Bigini, P +AU - Perini, P +AU - Bernardinello, D +AU - Cagnotto, A +AU - Mereghetti, I +AU - Curti, D +AU - Salmona, M +AU - Mennini, T +TI - Proteomic Profiling of Cervical and Lumbar Spinal Cord Reveals Potential Protective Mechanisms in the Wobbler Mouse, a Model of Motor Neuron Degeneration +T2 - JOURNAL OF PROTEOME RESEARCH +LA - English +KW - MALDI-TOF analysis +KW - motor neuron disease +KW - syntaxin-binding protein 1 +KW - vesicle fusing ATPase +KW - wobbler mouse +KW - AMYOTROPHIC-LATERAL-SCLEROSIS +KW - CENTRAL-NERVOUS-SYSTEM +KW - TRANSGENIC MICE +KW - AXONAL-TRANSPORT +KW - FAMILIAL ALS +KW - MURINE MODEL +KW - DISEASE +KW - PROTEINS +KW - ASTROCYTES +KW - NEURODEGENERATION +AB - The wobbler mouse is a model of selective motor neuron degeneration in the cervical spinal cord. Comparing cervical and lumbar tracts of control and diseased mice at the early stage of pathology by proteomic analysis, we identified 31 proteins by peptide mass fingerprint after tryptic digestion and MALDI-TOF analysis, that were differently represented among the four experimental groups. In healthy mice, patterns of protein expression differed between cervical and lumbar tract: proteins of cellular energetic metabolism pathway showed lower expression in the cervical tract, while cellular trafficking proteins were overrepresented. In wobbler mice, these differences disappeared and the expression pattern was similar between cervical and lumbar spinal cord. We found that most of the proteins differentially regulated in wobbler with respect to control cervical tract were related to astrogliosis or involved in glutamate-glutamine cycle, energy transduction and redox functions. Proteins overrepresented in the wobbler lumbar spinal cord were cytoskeleton proteins and cellular transport proteins, in particular the vesicle fusing ATPase and the isoform 2 of syntaxin-binding protein 1, involved in vesicle trafficking. We suggest that overexpression of proteins involved in vesicle trafficking, together with proteins counteracting mitochondrial dysfunction can have neuroprotective effects, preserving lumbar spinal cord motor neurons in wobbler mice. +AD - Ist Ric Farmacol Mario Negri, Dipartimento Biochim & Farmacol Mol, I-20156 Milan, Italy AD - Univ Pavia, Dept Legal Med Forens & Pharmacotoxicol Sci A For, I-27100 Pavia, Italy C3 - Istituto di Ricerche Farmacologiche Mario Negri IRCCS C3 - University of Pavia FU - Carpi Foundation; Ministero della Salute +FX - This study was partly supported by Carpi Foundation (Grant GUARD) and Ministero della Salute (BIOMAR project). Authors thank Dr. Sara Barbera for technical support +PU - AMER CHEMICAL SOC +PI - WASHINGTON +PA - 1155 16TH ST, NW, WASHINGTON, DC 20036 USA +SN - 1535-3893 +SN - 1535-3907 +J9 - J PROTEOME RES +JI - J. Proteome Res. +DA - NOV +PY - 2009 +VL - 8 +IS - 11 +SP - 5229 +EP - 5240 +DO - 10.1021/pr900569d +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000276949600031 +N1 - Times Cited in Web of Science Core Collection: 12 +Total Times Cited: 13 +Cited Reference Count: 45 +ER - + +TY - JOUR +AU - Jiang, SS +AU - Nie, HB +AU - Hua, S +AU - Xie, M +AU - Xu, RS +TI - Preliminary Analysis of Potentially Overlapping Differentially Expressed Proteins in Both the Spinal Cord and Brain of SOD1 G93A Mice +T2 - CURRENT PROTEIN & PEPTIDE SCIENCE +LA - English +KW - Preliminary analysis +KW - proteomic elucidation +KW - neurodegenerative disease +KW - mitochondrial dysfunction +KW - calcic influx +KW - amyotrophic lateral sclerosis +KW - AMYOTROPHIC-LATERAL-SCLEROSIS +KW - MOTOR-NEURON DEGENERATION +KW - CEREBROSPINAL-FLUID +KW - OXIDATIVE STRESS +KW - TRANSGENIC MICE +KW - PROTEOMIC ANALYSIS +KW - CSF BIOMARKERS +KW - MOUSE MODEL +KW - CYSTATIN-C +KW - ALS +AB - Objective Proteomic elucidation is an essential step in improving our understanding of the biological properties of proteins in amyotrophic lateral sclerosis (ALS).Methods Preliminary proteomic analysis was performed on the spinal cord and brain of SOD1 G93A (TG) and wild-type (WT) mice using isobaric tags for relative and absolute quantitation.Results Partial up- and downregulated proteins showing significant differences between TG and WT mice were identified, of which 105 proteins overlapped with differentially expressed proteins in both the spinal cord and brain of progression mice. Bioinformatic analyses using Gene Ontology, a cluster of orthologous groups, and Kyoto Encyclopedia of Genes and Genomes pathway revealed that the significantly up- and downregulated proteins represented multiple biological functions closely related to ALS, with 105 overlapping differentially expressed proteins in the spinal cord and brain at the progression stage of TG mice closely related to 122 pathways. Differentially expressed proteins involved in a set of molecular functions play essential roles in maintaining neural cell survival.Conclusion This study provides additional proteomic profiles of TG mice, including potential overlapping proteins in both the spinal cord and brain that participate in pathogenesis, as well as novel insights into the up- and downregulation of proteins involved in the pathogenesis of ALS. +AD - Nanchang Med Coll, Jiangxi Prov Peoples Hosp, Dept Neurol, Affiliated Hosp 1,Clin Coll, Nanchang 330006, Jiangxi, Peoples R China AD - Nanchang Med Coll, Jiangxi Prov Peoples Hosp, Affiliated Hosp 1, Dept Ultrasonog, Nanchang 330006, Jiangxi, Peoples R China AD - Nanchang Med Coll, Affiliated Hosp 1, Jiangxi Prov Peoples Hosp, Hlth Management Ctr, Nanchang 330006, Jiangxi, Peoples R China C3 - Nanchang Medical College C3 - Nanchang Medical College C3 - Nanchang Medical College FU - National Natural Science Foundation of China [30560042, 81160161, 81360198, 82160255]; Education Department of Jiangxi Province [GJJ13198, GJJ170021]; Jiangxi provincial department of science and technology [[2014]-47, 20142BBG70062, 20171-BAB-215022, 20192BAB205043]; Health and Family Planning Commission of Jiangxi province [20181019, 202210002, 202310119]; Jiangxi Provincial Department of Science and Technology Gan Po Elite 555 [[2015] 108] +FX - This study was partly supported by the research grants from the committee of the National Natural Science Foundation of China (30560042, 81160161, 81360198 and 82160255), Education Department of Jiangxi Province (GJJ13198 and GJJ170021), Jiangxi provincial department of science and technology ([2014]-47, 20142BBG70062, 20171BAB-215022 and 20192BAB205043), Health and Family Planning Commission of Jiangxi province (20181019, 202210002 and 202310119) and Jiangxi Provincial Department of Science and Technology Gan Po Elite 555 (Jiangxi Finance Elite Education Refers to [2015] 108). +PU - BENTHAM SCIENCE PUBL LTD +PI - SHARJAH +PA - EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES +SN - 1389-2037 +SN - 1875-5550 +J9 - CURR PROTEIN PEPT SC +JI - Curr. Protein Pept. Sci. +PY - 2025 +VL - 26 +IS - 1 +SP - 57 +EP - 75 +DO - 10.2174/0113892037293525240621120033 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001373855900001 +N1 - Times Cited in Web of Science Core Collection: 0 +Total Times Cited: 0 +Cited Reference Count: 107 +ER - + +TY - JOUR +AU - Li, WJ +AU - Pan, SQ +AU - Zeng, YS +AU - Su, BG +AU - Li, SM +AU - Ding, Y +AU - Li, Y +AU - Ruan, JW +TI - Identification of acupuncture-specific proteins in the process of electro-acupuncture after spinal cord injury +T2 - NEUROSCIENCE RESEARCH +LA - English +KW - Spinal cord injury +KW - Electro-acupuncture +KW - Neuroprotection +KW - Neuronal survival +KW - Clarke's nucleus +KW - CLARKES NUCLEUS NEURONS +KW - ANNEXIN-V +KW - DIFFERENTIAL EXPRESSION +KW - HIPPOCAMPAL-NEURONS +KW - PROTEOMIC ANALYSIS +KW - NEUROPATHIC PAIN +KW - CLINICAL-TRIAL +KW - STEM-CELLS +KW - GUIDANCE +KW - EPIDEMIOLOGY +AB - Spinal cord injury (SCI) is a serious condition often affecting young and healthy individuals around the world. Electro-acupuncture (EA) has been proven to contribute towards neurologic and functional recoveries in SCI, but the underlying mechanism remains largely unknown especially regarding neural specific proteins involved in the development of EA. The protein expression profile of spinal cord in both SCI and EA treatment models was analyzed by using two-dimensional electrophoresis-based proteomics. Using a MALDI-TOF/TOF MS and subsequent protein database searching, we identified changes in 15 proteins in the spinal cord following Governor Vessel (CV) EA treatment on SCI. These proteins are involved in inflammation, cell adhesion and migration, signal transduction and apoptosis processes. We selected 2 proteins (ANXA5 and CRMP2) beneficial to neuronal survival and axonal regeneration, and further identified these protein changes using Western blot analysis. Subsequently, Nissl staining and immunofluorescence double labeling approaches were used to explore possible role of the two neural specific proteins in the process of GV-EA treatment on SCI. Our results suggest that ANXA5 and CRMP2 may be neural specific proteins in the process of GV-EA treatment on SCI. This work might contribute to the better understanding of the mechanism involved in EA treatment on SCI at protein levels and provide a new therapeutic strategy for SCI (C) 2010 Elsevier Ireland Ltd and the japan Neuroscience Society. All rights reserved. +AD - Sun Yat Sen Univ, Div Neurosci, Dept Histol & Embryol, Zhongshan Sch Med, Guangzhou 510080, Guangdong, Peoples R China AD - Sun Yat Sen Univ, Affiliated Hosp 1, Dept Acupuncture, Guangzhou 510080, Guangdong, Peoples R China AD - Jinan Univ, Coll Med, Dept Anat, Guangzhou 510632, Guangdong, Peoples R China AD - Sun Yat Sen Univ, Inst Spinal Cord Injury, Guangzhou 510120, Guangdong, Peoples R China C3 - Sun Yat Sen University C3 - Sun Yat Sen University C3 - Jinan University C3 - Sun Yat Sen University FU - Natural Science Foundation of Guangdong Province [07001682]; Chinese National Natural Science Foundation [30472132, 30973721]; Administrative Bureau of Chinese Traditional Medicine of Guangdong Province [1050167, 2007109] +FX - This work was supported by Natural Science Foundation of Guangdong Province (No. 07001682) to J.W. Ruan, and Chinese National Natural Science Foundation (No. 30472132; 30973721) and Research Grant of the Administrative Bureau of Chinese Traditional Medicine of Guangdong Province (No. 1050167; 2007109) to Y.S. Zeng. The authors are grateful to Professor Eng-Ang Ling, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, for his helpful comments on the manuscript. +PU - ELSEVIER IRELAND LTD +PI - CLARE +PA - ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND +SN - 0168-0102 +SN - 1872-8111 +J9 - NEUROSCI RES +JI - Neurosci. Res. +DA - AUG +PY - 2010 +VL - 67 +IS - 4 +SP - 307 +EP - 316 +DO - 10.1016/j.neures.2010.04.012 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000280726100005 +N1 - Times Cited in Web of Science Core Collection: 34 +Total Times Cited: 35 +Cited Reference Count: 44 +ER - + +TY - JOUR +AU - Sarkis, GA +AU - Mangaonkar, MD +AU - Moghieb, A +AU - Lelling, B +AU - Guertin, M +AU - Yadikar, H +AU - Yang, Z +AU - Kobeissy, F +AU - Wang, KKW +TI - The Application of Proteomics to Traumatic Brain and Spinal Cord Injuries +T2 - CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS +LA - English +KW - Traumatic brain injury +KW - Spinal cord injury neuroproteomics +KW - Mass spectrometry +KW - Mass spectrometry imaging +KW - Systems biology +KW - IMAGING MASS-SPECTROMETRY +KW - ASSISTED-LASER-DESORPTION/IONIZATION +KW - SYSTEMS BIOLOGY +KW - INFLAMMATORY CYTOKINES +KW - CEREBROSPINAL-FLUID +KW - PROTEIN EXPRESSION +KW - PROFILE CHANGES +KW - CATHEPSIN-B +KW - MOUSE-BRAIN +KW - TISSUE +AB - Traumatic brain injury (TBI) and traumatic spinal cord injury (SCI), collectively termed neurotrauma, are two parallel neurological conditions that can cause long-lasting neurological impairment and other comorbidities in patients, while at the same time, can create a high burden to society. To date, there are still no FDA-approved therapeutic interventions for either TBI or SCI. Recent advances in proteomic technologies, including tandem mass spectrometry, as well as imaging mass spectrometry, have enabled new approaches to study the differential proteome in TBI and SCI with the use of either animal disease models and/or biosamples from clinical observational studies. Thus, the applications of state-ofthe- art proteomic method hold promises in shedding light on identifying clinically useful neurotrauma "biomarkers" and/or in identifying distinct and, otherwise, unobvious systems pathways or "key drivers" that can be further exploited as new therapeutic intervention targets. +AD - Univ Florida, Neuroproteom & Biomarkers Res, Dept Psychiat, Program Neurotrauma, Gainesville, FL 32611 USA AD - Univ Florida, Dept Neurosci, Gainesville, FL 32611 USA AD - Univ Florida, Dept Physiol Sci, Gainesville, FL 32611 USA AD - Univ Florida, Dept Chem, Gainesville, FL 32611 USA AD - Univ Alexandria, Fac Sci, Dept Chem, Ibrahimia, POB 426, Alexandria 21321, Egypt AD - Biol Sci Div Integrat Omi, Pacif Northwest Natl Lab, 902 Battelle Blvd, Richland, WA 99352 USA C3 - State University System of Florida C3 - University of Florida C3 - State University System of Florida C3 - University of Florida C3 - State University System of Florida C3 - University of Florida C3 - State University System of Florida C3 - University of Florida C3 - Egyptian Knowledge Bank (EKB) C3 - Alexandria University C3 - United States Department of Energy (DOE) C3 - Pacific Northwest National Laboratory PU - SPRINGER +PI - NEW YORK +PA - 233 SPRING ST, NEW YORK, NY 10013 USA +SN - 1528-4042 +SN - 1534-6293 +J9 - CURR NEUROL NEUROSCI +JI - Curr. Neurol. Neurosci. Rep. +DA - MAR +PY - 2017 +VL - 17 +IS - 3 +C7 - 23 +DO - 10.1007/s11910-017-0736-z +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000397406600004 +N1 - Times Cited in Web of Science Core Collection: 22 +Total Times Cited: 24 +Cited Reference Count: 80 +ER - + +TY - JOUR +AU - Yan, J +AU - Zhang, LQ +AU - Li, L +AU - He, WX +AU - Liu, WJ +TI - Developmentally engineered bio-assemblies releasing neurotrophic exosomes guide in situ neuroplasticity following spinal cord injury +T2 - MATERIALS TODAY BIO +LA - English +KW - Bio-assemblies +KW - Exosome +KW - Developmentally engineered +KW - Neuroplasticity +KW - Spinal cord injury +KW - MESENCHYMAL STROMAL CELLS +KW - NEURAL STEM-CELLS +KW - BONE-MARROW +KW - TISSUE +KW - DAMAGE +AB - The emerging tissue-engineered bio-assemblies are revolutionizing the regenerative medicine, and provide a potential program to guarantee predictive performance of stem-cell-derived treatments in vivo and hence support their clinical translation. Mesenchymal stem cell (MSC) showed the attractive potential for the therapy of nervous system injuries, especially spinal cord injury (SCI), and yet failed to make an impact on clinical outcomes. Herein, under the guidance of the embryonic development theory that appropriate cellular coarctations or clustering are pivotal initiators for the formation of geometric and functional tissue structures, a developmentally engineered strategy was established to assemble DPMSCs into a bio-assembly termed Spinor through a three-level sequential induction programme including reductant, energy and mechanical force stimulation. Spinor exhibited similar geometric construction with spinal cord tissue and attain autonomy to released exosome with the optimized quantity and quality for suppressing cicatrization and inflammation and promoting axonal regeneration. As a spinal cord fascia and exosome mothership, Spinor guided the in-situ neuroplasticity of spinal cord in vivo, and caused the significant motor improvement, sensory recovery, and faster urinary reflex restoration in rats following SCI, while maintaining a highly favorable biosafety profile. Collectively, Spinor not only is a potentially clinical therapeutic paradigm as a living "exosome mothership" for revisiting Prometheus' Myth in SCI, but can be viewed allowing developmentally engineered manufacturing of biomimetic bio-assemblies with complex topology features and inbuilt biofunction attributes towards the regeneration of complex tissues including nervous system. +AD - Second Affiliated Hosp Xian Jiaotong Univ, Natl & Local Joint Engn Res Ctr Biodiagnosis & Bi, Xian 710004, Peoples R China AD - Second Affiliated Hosp Xian Jiaotong Univ, Inst Stem Cell & Regenerat Med, Xian 710004, Peoples R China AD - First Affiliated Hosp Xian Jiaotong Univ, Dept Med Oncol, Xian 710061, Peoples R China AD - First Affiliated Hosp Xian Jiaotong Univ, Dept Talent Highland, Xian 710061, Peoples R China FU - National Natural Science Foundation of China [81970915]; Thousand Talents Plan of Shaanxi Province; Natural Science Fund of Shaanxi for distinguished Young Scholars [2020JC33]; Natural Science Basic Research Plan in Shaanxi Province of China [2020JQ-092]; Key R&D program of Shaanxi Province [2019KW-074, 2021SF-033]; "Young Talent Support Plan" of Xi'an Jiaotong University +FX - This work was supported by National Natural Science Foundation of China (No. 81970915 for W. Liu), Thousand Talents Plan of Shaanxi Province (For W. He), Natural Science Fund of Shaanxi for distinguished Young Scholars (2020JC33), Natural Science Basic Research Plan in Shaanxi Province of China (No. 2020JQ-092) and Key R&D program of Shaanxi Province (No. 2019KW-074 and No. 2021SF-033) "The Young Talent Support Plan" of Xi'an Jiaotong University (For W. Liu and W. He). We thank Instrument Analysis Center of Xi'an Jiaotong University for their assistance with AFM and SEM analysis. We also appreciate the help of proteomic analysis from BioNovoGene (Suzhou) Co., Ltd. +PU - ELSEVIER +PI - AMSTERDAM +PA - RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS +SN - 2590-0064 +J9 - MATER TODAY BIO +JI - Mater. Today Bio +DA - DEC +PY - 2022 +VL - 16 +DO - 10.1016/j.mtbio.2022.100406 +C6 - AUG 2022 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000890622700007 +N1 - Times Cited in Web of Science Core Collection: 9 +Total Times Cited: 9 +Cited Reference Count: 48 +ER - + +TY - JOUR +AU - Skalnikova, HK +AU - Navarro, R +AU - Marsala, S +AU - Hrabakova, R +AU - Vodicka, P +AU - Gadher, SJ +AU - Kovarova, H +AU - Marsala, M +TI - Signaling proteins in spinal parenchyma and dorsal root ganglion in rat with spinal injury-induced spasticity +T2 - JOURNAL OF PROTEOMICS +LA - English +KW - Spinal cord trauma +KW - Spasticity +KW - Hyper-reflexia +KW - Proteomic profiling +KW - Dorsal root ganglia +KW - Spinal gray matter +KW - COLONY-STIMULATING FACTOR +KW - CORD-INJURY +KW - MECHANICAL ALLODYNIA +KW - MULTIPLE-SCLEROSIS +KW - PROTEOMIC ANALYSIS +KW - DOWN-REGULATION +KW - NERVOUS-SYSTEM +KW - KINASE +KW - PAIN +KW - EXPRESSION +AB - Development of progressive muscle spasticity resulting from spinal traumatic injury can be mediated by loss of local segmental inhibition and/or by an increased sensory afferent drive with resulting exacerbated a-motoneuron activity. To identify potential contributions of neuroactive substances in the development of such spasticity state, we employed a well-defined spinal injury-evoked spasticity rat model. Signaling molecules were analyzed in the spinal parenchyma below the level of spinal injury and in the corresponding dorsal root ganglion cells using Kinex (TM) antibody microarrays. The results uncovered the involvement of angiogenesis and neurodegeneration pathways together with direct cross-talk mediated by several hub proteins with SH-2 domains. At 2 and 5 weeks after transection, up-regulation of several proteins including CaMKIV, RON alpha and PKC delta as well as MAPK3/ERK1 phosphorylation was observed in the spinal ventral horns. Our results indicate that these signaling molecules and their neuronal effector systems cannot only play an important role in the initiation but also in the maintenance of spasticity states after spinal trauma. The exclusivity of specific protein changes observed in lumbar spinal parenchyma but not in dorsal root ganglia indicates that new treatment strategies should primarily target specific spinal segments to prevent or attenuate spasticity states. + Biological significance + Development of progressive muscle spasticity and rigidity represents a serious complication associated with spinal ischemic or traumatic injury. Signaling proteins, including their phosphorylation status, were analyzed in the spinal parenchyma below the level of spinal injury and in the corresponding dorsal root ganglion cells in a rat model of spinal injury using Kinex (TM) antibody microarrays. The results uncovered direct protein interaction mediated cross-talk between angiogenesis and neurodegeneration pathways, which may significantly contribute to the healing process in the damaged region. Importantly, we identified several target proteins exclusively observed in the spinal lumbar ventral horns, where such proteins may not only play an important role in the initiation but also in the maintenance of spasticity states after spinal trauma. Hence, potential new treatment strategies such as gene silencing or drug treatment should primarily target spinal parenchymal sites at and around the injury epicenter and most likely employ intrathecal or targeted spinal segment-specific vector or drug delivery. We believe that this work will stimulate future translational research, ultimately leading to the improvement of quality of life of patients with spinal traumatic injury. (C) 2013 Elsevier B.V. All rights reserved. +AD - Acad Sci Czech Republ, Inst Anim Physiol & Genet, Lab Biochem & Mol Biol Germ Cells, Vvi, Libechov, Czech Republic AD - Univ Calif San Diego, Dept Anesthesiol, San Diego, CA 92103 USA AD - Acad Sci Czech Republ, Inst Anim Physiol & Genet, Lab Cell Regenerat & Plast, Vvi, Libechov, Czech Republic AD - Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA AD - Life Technol, Frederick, MD USA AD - Slovak Acad Sci, Inst Neurobiol, Kosice 04001, Slovakia C3 - Czech Academy of Sciences C3 - Institute of Animal Physiology & Genetics of the Czech Academy of Sciences C3 - University of California System C3 - University of California San Diego C3 - Czech Academy of Sciences C3 - Institute of Animal Physiology & Genetics of the Czech Academy of Sciences C3 - Harvard University C3 - Massachusetts General Hospital C3 - Thermo Fisher Scientific C3 - Slovak Academy of Sciences FU - MEYS [ME10044]; NIH [NS051644]; TACR [TA01011466]; Institutional Research Concept [RV067985904]; Operational Program Research and Development for Innovations [CZ.1.05/2.1.00/03.0124] +FX - This work was supported in part by MEYS (ME10044; H.K.), NIH (NS051644; M.M.), TACR (TA01011466; HK), and Institutional Research Concept RV067985904 (IAPG, AS CR, v.v.i). Infrastructural part of this project was supported from the Operational Program Research and Development for Innovations (CZ.1.05/2.1.00/03.0124). +PU - ELSEVIER +PI - AMSTERDAM +PA - RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS +SN - 1874-3919 +SN - 1876-7737 +J9 - J PROTEOMICS +JI - J. Proteomics +DA - OCT 8 +PY - 2013 +VL - 91 +SP - 41 +EP - 57 +DO - 10.1016/j.jprot.2013.06.028 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000327906000004 +N1 - Times Cited in Web of Science Core Collection: 12 +Total Times Cited: 14 +Cited Reference Count: 73 +ER - + +TY - JOUR +AU - da Silva, BF +AU - Souza, GHMF +AU - lo Turco, EG +AU - Del Giudice, PT +AU - Soler, TB +AU - Spaine, DM +AU - Borrelli, M +AU - Gozzo, FC +AU - Pilau, EJ +AU - Garcia, JS +AU - Ferreira, CR +AU - Eberlin, MN +AU - Bertolla, RP +TI - Differential seminal plasma proteome according to semen retrieval in men with spinal cord injury +T2 - FERTILITY AND STERILITY +LA - English +KW - Biomarkers +KW - spinal cord injury +KW - seminal plasma +KW - proteomics +KW - functional enrichment +KW - PROSTAGLANDIN D-SYNTHASE +KW - SPERM MOTILITY +KW - VIBRATORY STIMULATION +KW - ELECTRIC-CURRENT +KW - PROSTATE +KW - ELECTROEJACULATION +KW - IDENTIFICATION +KW - SPERMATOZOA +KW - INFERTILITY +KW - MECHANISMS +AB - Objective: To evaluate protein expression profile and to quantify proteins present in seminal plasma from men with spinal cord injury (SCI) and healthy men without SCI. + Design: Experimental study. + Setting: University hospital. + Patient(s): Twelve SCI patients divided into two groups, six who underwent electroejaculation (EEJ) and six who underwent penile vibratory stimulation (PVS); and ten control subjects presenting normal sperm motility and concentration. + Intervention(s): EEJ and PVS. + Main Outcome Measure(s): The seminal plasma protein profile was analyzed by two proteomic strategies: data-independent label-free quantitative proteomics (MSE) and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (2D SDS-PAGE). + Result(s): A total of 638 different proteins were identified by MSE and 18 by 2D SDS-PAGE followed by tandem mass spectrometry. Interactome analysis showed key reproductive biologic processes-insemination, sperm and oocyte fusion, and acrosome reaction-related to all groups, as were triglyceride stimuli. Processes related to actin and muscle function and to iron oxidation, transportation, and homeostasis were found only in the EEJ and PVS groups; response to hydrogen peroxide and increased immune response was found only in the PVS group. + Conclusion(s): This study was able to demonstrate differential protein expression among control, PVS, and EEJ groups; SCI is responsible for alterations in seminal plasma protein profile leading to a deviation from homeostasis; proteins reported in both PVS and EEJ groups correlate with the pathophysiology of SCI-related infertility. (Fertil Steril (R) 2013; 100: 959-69. (C) 2013 by American Society for Reproductive Medicine.) +AD - Univ Fed Sao Paulo, Dept Surg, Div Urol, Human Reprod Sect, BR-04039060 Sao Paulo, Brazil AD - Waters Corp, Mass Spectrometry Applicat Res & Dev Lab, Sao Paulo, Brazil AD - Univ Estadual Campinas, Thomson Mass Spectrometry Lab, Campinas, Brazil AD - Univ Estadual Campinas, Inst Chem, Campinas, Brazil AD - Natl Inst Bioanalyt Sci & Technol, Sao Paulo, Brazil AD - Univ Estadual Maringa, Ctr Exact Sci, Dept Chem, Maringa, Parana, Brazil AD - Alfenas Fed Univ, Inst Exact Sci, Alfenas, Brazil C3 - Universidade Federal de Sao Paulo (UNIFESP) C3 - Universidade Estadual de Campinas C3 - Universidade Estadual de Campinas C3 - Universidade Estadual de Maringa C3 - Universidade Federal de Alfenas FU - Conselho Nacional de Desenvolvimento Cientifico e Tecnologico +FX - Supported by the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico. +PU - ELSEVIER SCIENCE INC +PI - NEW YORK +PA - 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA +SN - 0015-0282 +J9 - FERTIL STERIL +JI - Fertil. Steril. +DA - OCT +PY - 2013 +VL - 100 +IS - 4 +SP - 959 +EP - + +DO - 10.1016/j.fertnstert.2013.06.009 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000324995200029 +N1 - Times Cited in Web of Science Core Collection: 20 +Total Times Cited: 20 +Cited Reference Count: 56 +ER - + +TY - JOUR +AU - Olmsted, ZT +AU - Stigliano, C +AU - Marzullo, B +AU - Cibelli, J +AU - Horner, PJ +AU - Paluh, JL +TI - Fully Characterized Mature Human iPS- and NMP-Derived Motor Neurons Thrive Without Neuroprotection in the Spinal Contusion Cavity +T2 - FRONTIERS IN CELLULAR NEUROSCIENCE +LA - English +KW - spinal cord injury +KW - spinal motor neuron +KW - neuromesodermal progenitor +KW - oligodendrocyte progenitor cell +KW - neuron transplantation +KW - neuron survival +KW - neuron maturation +KW - contusion +KW - DOPAMINE NEURONS +KW - STEM-CELLS +KW - IN-VITRO +KW - TRANSPLANTATION +KW - INHIBITION +KW - CIRCUITS +KW - RECOVERY +KW - GRAFTS +KW - INJURY +KW - TISSUE +AB - Neural cell interventions in spinal cord injury (SCI) have focused predominantly on transplanted multipotent neural stem/progenitor cells (NSPCs) for animal research and clinical use due to limited information on survival of spinal neurons. However, transplanted NSPC fate is unpredictable and largely governed by injury-derived matrix and cytokine factors that are often gliogenic and inflammatory. Here, using a rat cervical hemicontusion model, we evaluate the survival and integration of hiPSC-derived spinal motor neurons (SMNs) and oligodendrocyte progenitor cells (OPCs). SMNs and OPCs were differentiated in vitro through a neuromesodermal progenitor stage to mimic the natural origin of the spinal cord. We demonstrate robust survival and engraftment without additional injury site modifiers or neuroprotective biomaterials. Ex vivo differentiated neurons achieve cervical spinal cord matched transcriptomic and proteomic profiles, meeting functional electrophysiology parameters prior to transplantation. These data establish an approach for ex vivo developmentally accurate neuronal fate specification and subsequent transplantation for a more streamlined and predictable outcome in neural cell-based therapies of SCI. +AD - SUNY Albany, Polytech Inst, Coll Nanoscale Sci, Nanobiosci Constellat, Albany, NY 12222 USA AD - SUNY Albany, Polytech Inst, Coll Engn, Nanobiosci Constellat, Albany, NY 12222 USA AD - Houston Methodist Res Inst, Ctr Neuroregenerat, Dept Neurosurg, Houston, TX USA AD - New York State Ctr Excellence Bioinformat & Life, SUNY Buffalo Genom & Bioinformat Core, Buffalo, NY USA AD - Michigan State Univ, Coll Agr & Nat Resources, Dept Anim Sci, E Lansing, MI 48824 USA AD - Michigan State Univ, Coll Vet Med, Dept Large Anim Clin Sci, E Lansing, MI 48824 USA C3 - State University of New York (SUNY) System C3 - University at Albany, SUNY C3 - State University of New York (SUNY) System C3 - University at Albany, SUNY C3 - Houston Methodist C3 - Michigan State University C3 - Michigan State University PU - FRONTIERS MEDIA SA +PI - LAUSANNE +PA - AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND +SN - 1662-5102 +J9 - FRONT CELL NEUROSCI +JI - Front. Cell. Neurosci. +DA - JAN 3 +PY - 2022 +VL - 15 +C7 - 725195 +DO - 10.3389/fncel.2021.725195 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000745149400001 +N1 - Times Cited in Web of Science Core Collection: 7 +Total Times Cited: 7 +Cited Reference Count: 57 +ER - + +TY - JOUR +AU - Ma, Q +AU - Chen, X +AU - Sun, JL +AU - Wang, L +AU - Jiang, WC +AU - Zhang, X +AU - Chen, SF +TI - Complete Freund's adjuvant-induced protein dysregulation correlated with mirror image pain as assessed by quantitative proteomics of the mouse spinal cord +T2 - BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS +LA - English +KW - Complete Freund's adjuvant +KW - Mirror image pain +KW - Quantitative proteomic +KW - PKC delta +KW - Patch clamp recording +KW - NEUROPATHIC PAIN +KW - KINASE-C +KW - MODEL +KW - ITRAQ +KW - CONTRIBUTES +AB - Inflammation or trauma occurring on one side of the body can cause pathological pain on the contralateral noninjured side in a phenomenon called mirror-image pain (MIP). Although some potential mechanisms involved in MIP have been reported, including those involving the immune system and glial cells as well as neural mechanisms, the molecular mechanisms are not well understood. In this study, we aimed to understand the molecular mechanisms in MIP using quantitative proteomics and whole-cell patch clamp recordings. Behavioral test results showed that complete Freund's adjuvant could induce MIP in the mice. The results of isobaric tags for relative and absolute quantification (iTRAQ) quantitative proteomics showed that 108 proteins were dysregulated, and these proteins may represent potential targets. Furthermore, bioinformatics analysis was applied to explore the potential molecular mechanisms during MIP after complete Freund's adjuvant (CFA) treatment. Parallel reaction monitoring (PRM) results showed that PKC delta and seven other dysregulated proteins were related to MIP after CFA treatment. Patch clamp recording results showed that CFA treatment could increase intrinsic excitability and spontaneous firing in spinal cord neurons during MIP. In summary, we found that CFA could induce MIP. The results of proteomic research on the spinal cord after CFA treatment could provide new insight into the molecular mechanisms of MIP. Moreover, the neuronal activity of spinal cord neurons was upregulated during MIP after CFA treatment. In summary, the results of the spinal cord proteomic profile provide a potential molecular mechanism for understanding MIP. (C) 2021 Published by Elsevier Inc. +AD - Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150001, Heilongjiang, Peoples R China AD - Southern Univ Sci & Technol, Sch Life Sci, Dept Biol, Shenzhen 518055, Peoples R China AD - Xiamen Univ, Dept Neurosurg, Affiliated Hosp 1, Xiamen 361003, Peoples R China AD - Xiamen Univ, Dept Reprod, Affiliated Hosp 1, Xiamen, Peoples R China AD - Luohu Dist Ctr Dis Control & Prevent, Shenzhen 518000, Peoples R China AD - Shenzhen Univ, Shenzhen Peoples Hosp 2, Dept Gastroenterol, Affiliated Hosp 1, Shenzhen 518000, Peoples R China C3 - Harbin Institute of Technology C3 - Southern University of Science & Technology C3 - Xiamen University C3 - Xiamen University C3 - Shenzhen University FU - Natural Science Foundation of Fujian Province, China [2019J01574]; Natural Science Founda-tion for Youths of Fujian Health and Family Planning Commission, China [2019-2-48]; Medical and Health Guidance Program of Xiamen City, China [3502Z20214ZD1021] +FX - This study was supported by the Natural Science Foundation of Fujian Province, China (2019J01574) , the Natural Science Founda-tion for Youths of Fujian Health and Family Planning Commission, China (2019-2-48) and the Medical and Health Guidance Program of Xiamen City, China (3502Z20214ZD1021) . +PU - ACADEMIC PRESS INC ELSEVIER SCIENCE +PI - SAN DIEGO +PA - 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA +SN - 0006-291X +SN - 1090-2104 +J9 - BIOCHEM BIOPH RES CO +JI - Biochem. Biophys. Res. Commun. +DA - JAN 22 +PY - 2022 +VL - 589 +SP - 23 +EP - 28 +DO - 10.1016/j.bbrc.2021.11.032 +C6 - DEC 2021 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000729421800004 +N1 - Times Cited in Web of Science Core Collection: 1 +Total Times Cited: 1 +Cited Reference Count: 29 +ER - + +TY - JOUR +AU - Rong, YL +AU - Wang, JX +AU - Hu, T +AU - Shi, ZM +AU - Lang, CD +AU - Liu, W +AU - Cai, WH +AU - Sun, YJ +AU - Zhang, F +AU - Zhang, WZ +TI - Ginsenoside Rg1 Regulates Immune Microenvironment and Neurological Recovery After Spinal Cord Injury Through MYCBP2 Delivery via Neuronal Cell-Derived Extracellular Vesicles +T2 - ADVANCED SCIENCE +LA - English +KW - extracellular vesicles +KW - ginsenoside Rg1 +KW - microglial polarization +KW - oxidative stress +KW - spinal cord injury +KW - OXIDATIVE STRESS +KW - UBIQUITIN LIGASE +KW - REPAIR +KW - POLARIZATION +KW - REGENERATION +KW - EXOSOMES +AB - Spinal cord injury (SCI) is a severe neurological condition that frequently leads to significant sensory, motor, and autonomic dysfunction. This study sought to delineate the potential mechanistic underpinnings of extracellular vesicles (EVs) derived from ginsenoside Rg1-pretreated neuronal cells (Rg1-EVs) in ameliorating SCI. These results demonstrated that treatment with Rg1-EVs substantially improved motor function in spinal cord-injured mice. Rg1-EVs enhance microglial polarization toward the M2 phenotype and repressed oxidative stress, thereby altering immune responses and decreasing inflammatory cytokine secretion. Moreover, Rg1-EVs substantially diminish reactive oxygen species accumulation and enhanced neural tissue repair by regulating mitochondrial function. Proteomic profiling highlighted a significant enrichment of MYCBP2 in Rg1-EVs, and functional assays confirmed that MYCBP2 knockdown counteracted the beneficial effects of Rg1-EVs in vitro and in vivo. Mechanistically, MYCBP2 is implicated in the ubiquitination and degradation of S100A9, thereby promoting microglial M2-phenotype polarization and reducing oxidative stress. Overall, these findings substantiated the pivotal role of Rg1-EVs in neuronal protection and functional recovery following SCI through MYCBP2-mediated ubiquitination of S100A9. This research offers novel mechanistic insights into therapeutic strategies against SCI and supports the clinical potential of Rg1-EVs. + The study reveals the potential mechanism by which extracellular vesicles (EVs) derived from ginsenoside Rg1-pretreated neuronal cells (Rg1-EVs) promote functional recovery after spinal cord injury. These findings demonstrate that Rg1-EVs enhance motor function recovery in mice by enhancing microglia's polarization toward the M2 phenotype and reducing oxidative stress, driven by MYCBP2-mediated ubiquitination and degradation of S100A9. image +AD - Univ Sci & Technol China, Affiliated Hosp USTC 1, Div Life Sci & Med, Dept Orthopaed,Ctr Leading Med & Adv Technol IHM, Hefei 230001, Anhui, Peoples R China AD - Shanghai Univ, Natl Ctr Translat Med Shanghai SHU Branch, Shanghai 200444, Peoples R China AD - Nanjing Med Univ, Affiliated Hosp 1, Dept Orthoped, Nanjing 210029, Jiangsu, Peoples R China AD - Naval Med Univ, Affiliated Hosp 2, Dept Orthoped, Shanghai 200003, Peoples R China C3 - Chinese Academy of Sciences C3 - University of Science & Technology of China, CAS C3 - Shanghai University C3 - Nanjing Medical University C3 - Naval Medical University FU - Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM [2023IHM02008, 2023IHM01071]; New Medicine of University of Science and Technology of China [YD9110002020]; Foundation of National Center for Translational Medicine (Shanghai) SHU Branch [SUITM-202408] +FX - This work was supported by "Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM" (grant No. 2023IHM02008, 2023IHM01071), New Medicine of University of Science and Technology of China (grant No. YD9110002020), and the Foundation of National Center for Translational Medicine (Shanghai) SHU Branch (NO. SUITM-202408). +PU - WILEY +PI - HOBOKEN +PA - 111 RIVER ST, HOBOKEN 07030-5774, NJ USA +SN - 2198-3844 +J9 - ADV SCI +JI - Adv. Sci. +DA - 2024 JUN 19 +PY - 2024 +DO - 10.1002/advs.202402114 +C6 - JUN 2024 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001249865200001 +N1 - Times Cited in Web of Science Core Collection: 0 +Total Times Cited: 0 +Cited Reference Count: 51 +ER - + +TY - JOUR +AU - Byström, S +AU - Ayoglu, B +AU - Häggmark, A +AU - Mitsios, N +AU - Hong, MG +AU - Drobin, K +AU - Forsström, B +AU - Fredolini, C +AU - Khademi, M +AU - Amor, S +AU - Uhlén, M +AU - Olsson, T +AU - Mulder, J +AU - Nilsson, P +AU - Schwenk, JM +TI - Affinity Proteomic Profiling of Plasma, Cerebrospinal Fluid, and Brain Tissue within Multiple Sclerosis +T2 - JOURNAL OF PROTEOME RESEARCH +LA - English +KW - antibodies +KW - suspension bead arrays +KW - plasma +KW - CSF +KW - brain tissue +KW - immunofluorescence +KW - multiple sclerosis +KW - DIAGNOSTIC-CRITERIA +KW - MESSENGER-RNA +KW - ANTIBODY +KW - EXPRESSION +KW - BIOMARKERS +KW - LESIONS +KW - IRF8 +KW - SUSCEPTIBILITY +KW - INTEGRATION +KW - REAGENTS +AB - The brain is a vital organ and because it is well shielded from the outside environment, possibilities for noninvasive analysis are often limited. Instead, fluids taken from the spinal cord or circulatory system are preferred sources for the discovery of candidate markers within neurological diseases. In the context of multiple sclerosis (MS), we applied an affinity proteomic strategy and screened 22 plasma samples with 4595 antibodies (3450 genes) on bead arrays, then defined 375 antibodies (334 genes) for targeted analysis in a set of 172 samples and finally used 101 antibodies (43 genes) on 443 plasma as well as 573 cerebrospinal spinal fluid (CSF) samples. This revealed alteration of protein profiles in relation to MS subtypes for IRF8, IL7, METTL14, SLC30A7, and GAP43. Respective antibodies were subsequently used for immunofluorescence on human post-mortem brain tissue with MS pathology for expression and association analysis. There, antibodies for IRF8, IL7, and METTL14 stained neurons in proximity of lesions, which highlighted these candidate protein targets for further studies within MS and brain tissue. The affinity proteomic translation of profiles discovered by profiling human body fluids and tissue provides a powerful strategy to suggest additional candidates to studies of neurological disorders. +AD - KTH Royal Inst Technol, Sch Biotechnol, SciLifeLab, S-17121 Stockholm, Sweden AD - Karolinska Inst, SciLifeLab, Dept Neurosci, S-17177 Stockholm, Sweden AD - Karolinska Inst, Dept Clin Neurosci, Neuroimmunol Unit, S-17177 Stockholm, Sweden AD - Vrije Univ Amsterdam Med Ctr, Dept Pathol, NL-1081 HV Amsterdam, Netherlands C3 - SciLifeLab C3 - Royal Institute of Technology C3 - SciLifeLab C3 - Karolinska Institutet C3 - Karolinska Institutet C3 - Vrije Universiteit Amsterdam C3 - VU UNIVERSITY MEDICAL CENTER FU - Swedish Research Council; Swedish Brain Foundation; AFA Foundation; SciLifeLab; Knut and Alice Wallenberg Foundation +FX - We thank the whole group of Biobank Profiling-Affinity Proteomics at SciLifeLab Stockholm and the entire staff of the Human Protein Atlas for their efforts in generating the antibodies. We also thank the clinical teams and biobank staff who helped with sample collection. We thank Hjalmar Brismar and Hans Blom at SciLifeLab for providing access to microscopes. This work was supported by grants from the Swedish Research Council, the Swedish Brain Foundation, the AFA Foundation, as well as SciLifeLab and the Knut and Alice Wallenberg Foundation. +PU - AMER CHEMICAL SOC +PI - WASHINGTON +PA - 1155 16TH ST, NW, WASHINGTON, DC 20036 USA +SN - 1535-3893 +SN - 1535-3907 +J9 - J PROTEOME RES +JI - J. Proteome Res. +DA - NOV +PY - 2014 +VL - 13 +IS - 11 +SP - 4607 +EP - 4619 +DO - 10.1021/pr500609e +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000344636500012 +N1 - Times Cited in Web of Science Core Collection: 39 +Total Times Cited: 42 +Cited Reference Count: 64 +ER - + +TY - JOUR +AU - Linke, B +AU - Pierre, S +AU - Coste, O +AU - Angioni, C +AU - Becker, W +AU - Maier, TJ +AU - Steinhilber, D +AU - Wittpoth, C +AU - Geisslinger, G +AU - Scholich, K +TI - Toponomics Analysis of Drug-Induced Changes in Arachidonic Acid-Dependent Signaling Pathways during Spinal Nociceptive Processing +T2 - JOURNAL OF PROTEOME RESEARCH +LA - English +KW - Toponome +KW - protein networks +KW - immunohistochemistry +KW - dipyrone +KW - lipoxygenase +KW - arachidonic acid +KW - pain +KW - spinal cord +KW - PROSTAGLANDIN E-2 +KW - 5-LIPOXYGENASE ACTIVITY +KW - PROTEOMIC ANALYSIS +KW - LIPID MEDIATORS +KW - PROTEIN +KW - CELLS +KW - 12-LIPOXYGENASE +KW - DIPYRONE +KW - PAIN +KW - CYCLOOXYGENASE +AB - Multi-Epitope-Ligand-Carthography (MELC) allows consecutive immunohistochemical visualization of up to 100 proteins on the same tissue sample. Subsequent biomathematical analysis of these images allows a quantitative description of changes in protein networks. We used the MELC technology to study the effect of the nonopioid analgesic drug dipyrone on protein network profiles associated with arachidonic acid-dependent signaling pathways. MELC analysis with 31 different fluorescence-labeled tags was used to compare the effect of dipyrone on protein networks in spinal cords of mice with zymosan-induced hyperalgesia, a common model for inflammatory pain. We found that the number of motifs which describe the colocalization of 5-lipoxygenase (5-LO) or 12-LO with other proteins increased disproportionally after dipyrone treatment. Activation of 5-LO and 12-LO induces their translocation to membrane compartments which was also reflected by MELC results. Although no changes in 5-LO or 12-LO expression were seen by Western blot analysis or by immunohistochemistry in spinal cords of dipyrone-treated mice, the activation of both enzymes was verified by determining LO-products. Spinal amounts of 5(S)-hydroxyeicosatetraenoic acid (HETE) and 12(S)-HETE, which are generated by 5-LO and 12-LO, respectively, were significantly increased in spinal cords of dipyrone-treated animals. In primary spinal cord neurons, dipyrone selectively and dose-dependently increased 5(S)-(HETE) and 12(S)-HETE synthesis. Thus, we show for the first time that monitoring protein network profiles by topological proteomic analysis is a useful tool to identify mechanisms of drug actions. +AD - Klinikum Goethe Univ Frankfurt, Inst Clin Pharmacol, ZAFES, Pharmazentrum Frankfurt, D-60590 Frankfurt, Germany AD - Goethe Univ Frankfurt, Inst Pharmaceut Chem, D-6000 Frankfurt, Germany AD - MelTec GmbH&Co KG, Magdeburg, Germany C3 - Goethe University Frankfurt C3 - Goethe University Frankfurt Hospital C3 - Goethe University Frankfurt FU - DFG [SCHO817-1, SCHO817-2]; LOEWE Lipid Signaling Forschungszentrum Frankfurt (LIFF); [GE695] +FX - The work was supported by the DFG grants SCHO817-1 and -2, GE695 and the LOEWE Lipid Signaling Forschungszentrum Frankfurt (LIFF). We would like to thank Lars Philipsen and Alexis Beyer, MelTec GmbH& Co KG, Magdeburg, for their advice and the technical support with the MELC technology. +PU - AMER CHEMICAL SOC +PI - WASHINGTON +PA - 1155 16TH ST, NW, WASHINGTON, DC 20036 USA +SN - 1535-3893 +SN - 1535-3907 +J9 - J PROTEOME RES +JI - J. Proteome Res. +DA - OCT +PY - 2009 +VL - 8 +IS - 10 +SP - 4851 +EP - 4859 +DO - 10.1021/pr900106v +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000270353900042 +N1 - Times Cited in Web of Science Core Collection: 23 +Total Times Cited: 23 +Cited Reference Count: 39 +ER - + +TY - JOUR +AU - DeBartolo, D +AU - Arnold, FJ +AU - Liu, YH +AU - Molotsky, E +AU - Tang, HY +AU - Merry, DE +TI - Differentially disrupted spinal cord and muscle energy metabolism in spinal and bulbar muscular atrophy +T2 - JCI INSIGHT +LA - English +KW - RECESSIVE BULBOSPINAL NEURONOPATHY +KW - STIMULATED INSULIN-SECRETION +KW - ANDROGEN RECEPTOR +KW - MOUSE MODEL +KW - NICOTINAMIDE RIBOSIDE +KW - FATTY LIVER +KW - DIPHOSPHOPYRIDINE NUCLEOTIDE +KW - SKELETAL-MUSCLE +KW - GENE-EXPRESSION +KW - NUCLEAR EXPORT +AB - Prior studies showed that polyglutamine-expanded androgen receptor (AR) is aberrantly acetylated and that deacetylation of the mutant AR by overexpression of nicotinamide adenine dinucleotide-dependent (NAD+-dependent) sirtuin 1 is protective in cell models of spinal and bulbar muscular atrophy (SBMA). Based on these observations and reduced NAD+ in muscles of SBMA mouse models, we tested the therapeutic potential of NAD+ restoration in vivo by treating postsymptomatic transgenic SBMA mice with the NAD+ precursor nicotinamide riboside (NR). NR supplementation failed to alter disease progression and had no effect on increasing NAD+ or ATP content in muscle, despite producing a modest increase of NAD+ in the spinal cords of SBMA mice. Metabolomic and proteomic profiles of SBMA quadriceps muscles indicated alterations in several important energy -related pathways that use NAD+, in addition to the NAD+ salvage pathway, which is critical for NAD+ regeneration for use in cellular energy production. We also observed decreased mRNA levels of nicotinamide riboside kinase 2 (Nmrk2), which encodes a key kinase responsible for NR phosphorylation, allowing its use by the NAD+ salvage pathway. Together, these data suggest a model in which NAD+ levels are significantly decreased in muscles of an SBMA mouse model and intransigent to NR supplementation because of decreased levels of Nmrk2. +AD - Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA AD - Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, Prote & Metabol Shared Resource, Philadelphia, PA USA AD - Thomas Jefferson Univ, 411E Jefferson Alumni Hall,1020 Locust St, Philadelphia, PA 19107 USA AD - Univ Calif Irvine, Sch Med, Dept Pathol & Lab Med, Irvine, CA USA AD - Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA C3 - Thomas Jefferson University C3 - The Wistar Institute C3 - Thomas Jefferson University C3 - University of California System C3 - University of California Irvine C3 - Johns Hopkins University FU - National Cancer Institute of the NIH [P30CA056036]; NIH [R01 NS090335, R01 NS106302] +FX - We thank members of the Merry lab for helpful discussions. Research reported in this publication used the Bioimaging Facility, with the support of Maria Covarrubias, at Sidney Kimmel Cancer Center at Thom-as Jefferson University, which was supported by the National Cancer Institute of the NIH under award P30CA056036. This work was supported by NIH grants R01 NS090335 and R01 NS106302. +PU - AMER SOC CLINICAL INVESTIGATION INC +PI - ANN ARBOR +PA - 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA +SN - 2379-3708 +J9 - JCI INSIGHT +JI - JCI Insight +DA - MAR 7 +PY - 2024 +VL - 9 +IS - 7 +C7 - e178048 +DO - 10.1172/jci.insight.178048 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001201710900001 +N1 - Times Cited in Web of Science Core Collection: 1 +Total Times Cited: 1 +Cited Reference Count: 95 +ER - + +TY - JOUR +AU - Ahn, JJ +AU - Miller, RH +AU - Islam, Y +TI - Isolation of Pure Astrocytes and Microglia from the Adult Mouse Spinal Cord For In Vitro Assays and Transcriptomic Studies +T2 - JOVE-JOURNAL OF VISUALIZED EXPERIMENTS +LA - English +KW - BRAIN +AB - Astrocytes and microglia play pivotal roles in central nervous system development, injury responses, and neurodegenerative diseases. These highly dynamic cells exhibit rapid responses to environmental changes and display significant heterogeneity in terms of morphology, transcriptional profiles, and functions. While our understanding of the functions of glial cells in health and disease has advanced substantially, there remains a need for in vitro, cell-specific analyses conducted in the context of insults or injuries to comprehensively characterize distinct cell populations. Isolating cells from the adult mouse offers several advantages over cell lines or neonatal animals, as it allows for the analysis of cells under pathological conditions and at specific time points. Furthermore, focusing on spinal cord-specific isolation, excluding brain involvement, enables research into spinal cord pathologies, including experimental autoimmune encephalomyelitis, spinal cord injury, and amyotrophic lateral sclerosis. This protocol presents an efficient method for isolating astrocytes and microglia from the adult mouse spinal cord, facilitating immediate or future analysis with potential applications in functional, molecular, or proteomic downstream studies. +AD - George Washington Univ, Dept Anat & Cell Biol, Sch Med, Washington, DC 20052 USA C3 - George Washington University FU - National Institute of Neurological Disorders and Stroke [F31NS117085]; Vivian Gill Research Endowment +FX - We thank Castle Raley at the George Washington University Genomics Core for RNA analyses and Q2 Lab Solutions for RNA sequencing analyses. This work was supported by the National Institute of Neurological Disorders and Stroke [grant number F31NS117085] and the Vivian Gill Research Endowment to Dr. Robert H. Miller. Figure 1 was created withBioRender.com. +PU - JOURNAL OF VISUALIZED EXPERIMENTS +PI - CAMBRIDGE +PA - 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA +SN - 1940-087X +J9 - JOVE-J VIS EXP +JI - J. Vis. Exp. +DA - OCT +PY - 2023 +IS - 200 +C7 - e65893 +DO - 10.3791/65893 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001100307000018 +N1 - Times Cited in Web of Science Core Collection: 0 +Total Times Cited: 0 +Cited Reference Count: 19 +ER - + +TY - JOUR +AU - Devaux, S +AU - Cizkova, D +AU - Mallah, K +AU - Karnoub, MA +AU - Laouby, Z +AU - Kobeissy, F +AU - Blasko, J +AU - Nataf, S +AU - Pays, L +AU - Mériaux, C +AU - Fournier, I +AU - Salzet, M +TI - RhoA Inhibitor Treatment At Acute Phase of Spinal Cord Injury May Induce Neurite Outgrowth and Synaptogenesis +T2 - MOLECULAR & CELLULAR PROTEOMICS +LA - English +KW - BAF MSWI/SNF COMPLEXES +KW - GROWTH CONE COLLAPSE +KW - AXON REGENERATION +KW - PROTEOMIC ANALYSIS +KW - IN-VIVO +KW - CELLS +KW - P53 +KW - QUANTIFICATION +KW - EXPRESSION +KW - RECOVERY +AB - The therapeutic use of RhoA inhibitors (RhoAi) has been experimentally tested in spinal cord injury (SCI). In order to decipher the underlying molecular mechanisms involved in such a process, an in vitro neuroproteomic-systems biology platform was developed in which the pan-proteomic profile of the dorsal root ganglia (DRG) cell line ND7/23 DRG was assessed in a large array of culture conditions using RhoAi and/or conditioned media obtained from SCI ex vivo derived spinal cord slices. A fine mapping of the spatio-temporal molecular events of the RhoAi treatment in SCI was performed. The data obtained allow a better understanding of regeneration/degeneration induced above and below the lesion site. Results notably showed a time-dependent alteration of the transcription factors profile along with the synthesis of growth cone-related factors (receptors, ligands, and signaling pathways) in RhoAi treated DRG cells. Furthermore, we assessed in a rat SCI model the in vivo impact of RhoAi treatment administered in situ via alginate scaffold that was combined with FK506 delivery. The improved recovery of locomotion was detected only at the early postinjury time points, whereas after overall survival a dramatic increase of synaptic contacts on outgrowing neurites in affected segments was observed. We validate these results by in vivo proteomic studies along the spinal cord segments from tissue and secreted media analyses, confirming the increase of the synaptogenesis expression factors under RhoAi treatment. Taken together, we demonstrate that RhoAi treatment seems to be useful to stimulate neurite outgrowth in both in vitro as well in vivo environments. However, for in vivo experiments there is a need for sustained delivery regiment to facilitate axon regeneration and promote synaptic reconnections with appropriate target neurons also at chronic phase, which in turn may lead to higher assumption for functional improvement. +AD - Univ Lille, INSERM, U1192, Lab Prote Reponse Inflammatoire & Spectrometrie M, F-59000 Lille, France AD - Slovak Acad Sci, Inst Neuroimmunol, Dubravska Cesta 9, Bratislava 84510, Slovakia AD - Univ Vet Med & Pharm Kosice, Dept Anat Histol & Physiol, Komenskeho 73, Kosice 04181, Slovakia AD - Amer Univ Beirut, Dept Biochem & Mol Genet, Fac Med, Beirut, Lebanon AD - Slovak Acad Sci, Inst Neurobiol, Soltesovej 4-6, Kosice, Slovakia AD - Univ Claude Bernard Lyon 1, CarMeN Lab, Inserm U1060, INRA U1397,INSA Lyon,Charles Merieux Med Sch, FR-69600 Oullins, France C3 - Institut National de la Sante et de la Recherche Medicale (Inserm) C3 - Universite de Lille C3 - Slovak Academy of Sciences C3 - University of Veterinary Medicine Kosice C3 - American University of Beirut C3 - Slovak Academy of Sciences C3 - Universite Claude Bernard Lyon 1 C3 - Institut National de la Sante et de la Recherche Medicale (Inserm) C3 - Institut National des Sciences Appliquees de Lyon - INSA Lyon C3 - INRAE FU - Fundamental and Applied Biology Mass Spectrometry Laboratory; Ministere de L'Education Nationale, L'Enseignement Superieur et de la Recherche; INSERM; Region Nord-Pas de Calais; SIRIC ONCOLille [INCa-DGOS-Inserm 6041aa]; Universite de Lille 1; VEGA [2/0125/15]; APVV [SK-FR-2015-0018]; [APVV-15-0613] +FX - This research was supported by a collaboration between the Fundamental and Applied Biology Mass Spectrometry Laboratory (MS) and grants from Ministere de L'Education Nationale, L'Enseignement Superieur et de la Recherche, INSERM, Region Nord-Pas de Calais (to SD), SIRIC ONCOLille Grant INCa-DGOS-Inserm 6041aa (IF) and Universite de Lille 1 (SD), APVV-15-0613 (DC), VEGA 2/0125/15, Stefanik (MS) APVV SK-FR-2015-0018 (DC). +PU - AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC +PI - BETHESDA +PA - 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA +SN - 1535-9476 +SN - 1535-9484 +J9 - MOL CELL PROTEOMICS +JI - Mol. Cell. Proteomics +DA - AUG +PY - 2017 +VL - 16 +IS - 8 +SP - 1394 +EP - 1415 +DO - 10.1074/mcp.M116.064881 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000406638100001 +N1 - Times Cited in Web of Science Core Collection: 22 +Total Times Cited: 24 +Cited Reference Count: 53 +ER - + +TY - JOUR +AU - Abdullah, L +AU - Crynen, G +AU - Reed, J +AU - Bishop, A +AU - Phillips, J +AU - Ferguson, S +AU - Mouzon, B +AU - Mullan, M +AU - Mathura, V +AU - Mullan, M +AU - Ait-Ghezala, G +AU - Crawford, F +TI - Proteomic CNS Profile of Delayed Cognitive Impairment in Mice Exposed to Gulf War Agents +T2 - NEUROMOLECULAR MEDICINE +LA - English +KW - Cognitive impairment +KW - Proteomic +KW - Astrogliosis +KW - Gulf War illness +KW - ACID-BINDING PROTEIN +KW - CENTRAL-NERVOUS-SYSTEM +KW - PYRIDOSTIGMINE BROMIDE +KW - REACTIVE ASTROCYTES +KW - IMMUNE FUNCTION +KW - SPINAL-CORD +KW - BRAIN +KW - VETERANS +KW - PERMETHRIN +KW - SYMPTOMS +AB - Gulf War Illness (GWI) is a chronic multisymptom condition with a central nervous system (CNS) component, for which there is no treatment available. It is now believed that the combined exposure to Gulf War (GW) agents, including pyridostigmine bromide (PB) and pesticides, such as permethrin (PER), was a key contributor to the etiology of GWI. In this study, a proteomic approach was used to characterize the biomolecular disturbances that accompany neurobehavioral and neuropathological changes associated with combined exposure to PB and PER. Mice acutely exposed to PB and PER over 10 days showed an increase in anxiety-like behavior, psychomotor problems and delayed cognitive impairment compared to control mice that received vehicle only. Proteomic analysis showed changes in proteins associated with lipid metabolism and molecular transport in the brains of GW agent-exposed mice compared to controls. Proteins associated with the endocrine and immune systems were also altered, and dysfunction of these systems is a prominent feature of GWI. The presence of astrogliosis in the GW agent-exposed mice compared to control mice further suggests an immune system imbalance, as is observed in GWI. These studies provide a broad perspective of the molecular disturbances driving the late pathology of this complex illness. Evaluation of the potential role of these biological functions in GWI will be useful in identifying molecular pathways that can be targeted for the development of novel therapeutics against GWI. +AD - Roskamp Inst, Sarasota, FL 34243 USA AD - Open Univ, Milton Keynes MK7 6AA, Bucks, England AD - James A Haley VA Hosp, Tampa, FL 33612 USA C3 - Open University - UK FU - Congressionally Directed Medical Research Program award [GW080094] +FX - This work is supported by a Congressionally Directed Medical Research Program award to Dr. Fiona Crawford (Grant#: GW080094). +PU - HUMANA PRESS INC +PI - TOTOWA +PA - 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA +SN - 1535-1084 +SN - 1559-1174 +J9 - NEUROMOL MED +JI - Neuromol. Med. +DA - DEC +PY - 2011 +VL - 13 +IS - 4 +SP - 275 +EP - 288 +DO - 10.1007/s12017-011-8160-z +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000300355400005 +N1 - Times Cited in Web of Science Core Collection: 60 +Total Times Cited: 70 +Cited Reference Count: 64 +ER - + +TY - JOUR +AU - Parker, GC +AU - Carruthers, NJ +AU - Gratsch, T +AU - Caruso, JA +AU - Stemmer, PM +TI - Proteomic profile of embryonic stem cells with low survival motor neuron protein is consistent with developmental dysfunction +T2 - JOURNAL OF NEURAL TRANSMISSION +LA - English +KW - Spinal muscular atrophy +KW - Stem cells +KW - Mass spectrometry +KW - Proteomics +KW - SPINAL MUSCULAR-ATROPHY +KW - SINGLE NUCLEOTIDE +KW - GENE SMN1 +KW - HEDGEHOG +KW - DISEASE +KW - COMPLEX +KW - MODEL +KW - CORD +KW - SMA +AB - Spinal muscular atrophy is an autosomal recessive motor neuron disease caused by a genetic defect carried by as many as one in 75 people. Unlike most neurological disorders, we know exactly what the genetic basis is of the disorder, but in spite of this, have little understanding of why the low levels of one protein, survival motor neuron protein, results in the specific progressive die back of only one cell type in the body, the motor neuron. Given the fact that all cells in the body of a patient with spinal muscular atrophy share the same low abundance of the protein throughout development, an appropriate approach is to ask how lower levels of survival motor neuron protein affects the proteome of embryonic stem cells prior to development. Convergent biostatistical analyses of a discovery proteomic analysis of these cells provide results that are consistent with the pathomechanistic fate of the developed motor neuron. +AD - Wayne State Univ, Carman & Ann Adam Dept Pediat, Detroit, MI USA AD - Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI USA AD - iBio, 6135 Woodward Ave,Suite 2128 CURES H208, Detroit, MI 48202 USA C3 - Wayne State University C3 - Wayne State University FU - National Institutes of Health National Institute of Environmental Health Sciences [P30 ES020957, P30 CA022453, S10 OD010700]; National Institutes of Health National Institute of Neurological Disorders and Stroke [1R21NS071339]; Children's Hospital of Michigan Sarnaik fund +FX - This work was performed in the Wayne State University, Karmanos Cancer Center and Environmental Health Sciences CURES Center Proteomics Core that is supported by National Institutes of Health National Institute of Environmental Health Sciences P30 ES020957, P30 CA022453, and S10 OD010700. Stem cell culture was supported by National Institutes of Health National Institute of Neurological Disorders and Stroke 1R21NS071339 awarded to GCP and the Children's Hospital of Michigan Sarnaik fund. +PU - SPRINGER WIEN +PI - WIEN +PA - SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA +SN - 0300-9564 +SN - 1435-1463 +J9 - J NEURAL TRANSM +JI - J. Neural Transm. +DA - JAN +PY - 2017 +VL - 124 +IS - 1 +SP - 13 +EP - 23 +DO - 10.1007/s00702-016-1520-y +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000392516200003 +N1 - Times Cited in Web of Science Core Collection: 3 +Total Times Cited: 4 +Cited Reference Count: 38 +ER - + +TY - JOUR +AU - Elkabes, S +AU - Li, H +TI - Proteomic strategies in multiple sclerosis and its animal models +T2 - PROTEOMICS CLINICAL APPLICATIONS +LA - English +KW - autoimmune disease +KW - cerebrospinal fluid +KW - experimental autoimmune encephalomyelitis +KW - glia +KW - spinal cord inflammation +KW - APPEARING WHITE-MATTER +KW - MYELIN-OLIGODENDROCYTE GLYCOPROTEIN +KW - EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS +KW - MACROPHAGE-STIMULATING PROTEIN +KW - EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS +KW - HUMAN CEREBROSPINAL-FLUID +KW - ANTIBODY CROSS-LINKING +KW - CENTRAL-NERVOUS-SYSTEM +KW - CYSTATIN-C +KW - AXONAL DAMAGE +AB - The early and precise diagnosis, the prognosis, and the clinical management of multiple sclerosis, remain a considerable challenge. In recent years, the development of novel and powerful proteomic techniques prompted the use of these approaches for the search of unique biomarkers in the cerebrospinal fluid of multiple sclerosis patients. A few studies have also utilized proteomics to delineate the profile of differentially expressed proteins in animal models of the human disease in order to gain global insights into affected pathways. The identification of differentially expressed proteins may be an initial step in the discovery of novel targets and mechanisms that play critical roles in the pathology of multiple sclerosis. Based on these findings, future investigations may elucidate the events leading to demyelination, axonal damage, and neurodegeneration, providing better insights into mechanisms governing the onset and progression of the disease. Although these proteomic studies provide valuable information, they are also faced with a number of challenges. The present review discusses some of the strengths and limitations of proteomic investigations as applied to multiple sclerosis. +AD - Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ USA AD - Univ Med & Dent New Jersey, Ctr Canc, New Jersey Med Sch, Ctr Adv Proteom Res,Dept Biochem & Mol Biol, Newark, NJ USA C3 - Rutgers University System C3 - Rutgers University New Brunswick C3 - Rutgers University Biomedical & Health Sciences C3 - Rutgers University System C3 - Rutgers University New Brunswick C3 - Rutgers University Biomedical & Health Sciences FU - NINDS NIH HHS [R01 NS046363, R01 NS046363-04, P30 NS046593-04, P30 NS046593] Funding Source: Medline +PU - WILEY-V C H VERLAG GMBH +PI - WEINHEIM +PA - POSTFACH 101161, 69451 WEINHEIM, GERMANY +SN - 1862-8346 +SN - 1862-8354 +J9 - PROTEOM CLIN APPL +JI - Proteom. Clin. Appl. +DA - NOV +PY - 2007 +VL - 1 +IS - 11 +SP - 1393 +EP - 1405 +DO - 10.1002/prca.200700315 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000251022600007 +N1 - Times Cited in Web of Science Core Collection: 11 +Total Times Cited: 11 +Cited Reference Count: 128 +ER - + +TY - JOUR +AU - Verrier, L +AU - Davidson, L +AU - Gierlinski, M +AU - Dady, A +AU - Storey, KG +TI - Neural differentiation, selection and transcriptomic profiling of human neuromesodermal progenitor-like cells in vitro +T2 - DEVELOPMENT +LA - English +KW - Neuromesodermal progenitor-like cells +KW - Human neural development +KW - Human spinal cord +KW - Dual SMAD inhibition +KW - CRISPR-Cas9 +KW - Human ES cells +KW - Nkx1.2 reporter +KW - Human neuromesodermal progenitor transcriptome +KW - BODY AXIS +KW - NEURONAL DIFFERENTIATION +KW - EXPRESSION PATTERNS +KW - PRIMITIVE STREAK +KW - GENE-EXPRESSION +KW - STEM-CELLS +KW - WNT +KW - FGF +KW - SIGNALS +KW - INHIBITION +AB - Robust protocols for directed differentiation of human pluripotent cells are required to determine whether mechanisms operating in model organisms are relevant to our own development. Recent work in vertebrate embryos has identified neuromesodermal progenitors as a bipotent cell population that contributes to paraxial mesoderm and spinal cord. However, precise protocols for in vitro differentiation of human spinal cord progenitors are lacking. Informed by signalling in amniote embryos, we show here that transient dual-SMAD inhibition, together with retinoic acid (dSMADi-RA), provides rapid and reproducible induction of human spinal cord progenitors from neuromesodermal progenitor-like cells. Using CRISPR-Cas9 to engineer human embryonic stem cells with a GFP-reporter for neuromesodermal progenitor-associated gene NKx1.2 we facilitate selection of this cell population. RNA-sequencing was then used to identify human and conserved neuromesodermal progenitor transcriptional signatures, to validate this differentiation protocol and to reveal new pathways/processes in human neural differentiation. This optimised protocol, novel reporter line and transcriptomic data am useful resources with which to dissect molecular mechanisms regulating human spinal cord generation and allow the scaling-up of distinct cell populations for global analyses, including proteomic, biochemical and chromatin interrogation. +AD - Univ Dundee, Sch Life Sci, Div Cell & Dev Biol, Dow St, Dundee DD1 5EH, Scotland AD - Univ Dundee, Sch Life Sci, Div Cell & Dev Biol, Human Pluripotent Cell Facil, Dow St, Dundee DD1 5EH, Scotland AD - Univ Dundee, Sch Life Sci, Div Cell & Dev Biol, Data Anal Grp, Dow St, Dundee DD1 5EH, Scotland C3 - University of Dundee C3 - University of Dundee C3 - University of Dundee FU - Wellcome Trust [WT102817AIA] +FX - This research was supported by a Wellcome Trust Investigator Award to K.G.S. (WT102817AIA). Deposited in PMC for immediate release. +PU - COMPANY BIOLOGISTS LTD +PI - CAMBRIDGE +PA - BIDDER BUILDING, STATION RD, HISTON, CAMBRIDGE CB24 9LF, ENGLAND +SN - 0950-1991 +SN - 1477-9129 +J9 - DEVELOPMENT +JI - Development +DA - AUG +PY - 2018 +VL - 145 +IS - 16 +C7 - dev166215 +DO - 10.1242/dev.166215 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000443499500012 +N1 - Times Cited in Web of Science Core Collection: 37 +Total Times Cited: 42 +Cited Reference Count: 62 +ER - + +TY - JOUR +AU - Lukas, TJ +AU - Luo, WW +AU - Mao, HH +AU - Cole, N +AU - Siddique, T +TI - Informatics-assisted protein profiling in a transgenic mouse model of amyotrophic lateral sclerosis +T2 - MOLECULAR & CELLULAR PROTEOMICS +LA - English +KW - CU,ZN SUPEROXIDE-DISMUTASE +KW - SPINAL-CORD +KW - MUTANT SOD1 +KW - FAMILIAL ALS +KW - CELL-DEATH +KW - MITOCHONDRIAL LOCALIZATION +KW - DIFFERENTIAL EXPRESSION +KW - PHOSPHATASE EXPRESSION +KW - DISEASE PROGRESSION +KW - PROTEOMIC ANALYSIS +AB - One of the causes of amyotrophic lateral sclerosis (ALS) is due to mutations in Cu,Zn-superoxide dismutase (SOD1). The mutant protein exhibits a toxic gain of function that adversely affects the function of neurons in the spinal cord, brain stem, and motor cortex. A proteomic analysis of protein expression in a widely used mouse model of ALS was undertaken to identify differences in protein expression in the spinal cords of mice expressing a mutant protein with the G93A mutation found in human ALS. Protein profiling was done on soluble and particulate fractions of spinal cord extracts using high throughput two-dimensional liquid chromatography coupled to tandem mass spectrometry. An integrated proteomics-informatics platform was used to identify relevant differences in protein expression based upon the abundance of peptides identified by database searching of mass spectrometry data. Changes in the expression of proteins associated with mitochondria were particularly prevalent in spinal cord proteins from both mutant G93A-SOD1 and wild-type SOD1 transgenic mice. G93A-SOD1 mouse spinal cord also exhibited differences in proteins associated with metabolism, protein kinase regulation, antioxidant activity, and lysosomes. Using gene ontology analysis, we found an overlap of changes in mRNA expression in presymptomatic mice (from microarray analysis) in three different gene categories. These included selected protein kinase signaling systems, ATP-driven ion transport, and neurotransmission. Therefore, alterations in selected cellular processes are detectable before symptomatic onset in ALS mouse models. However, in late stage disease, mRNA expression analysis did not reveal significant changes in mitochondrial gene expression but did reveal concordant changes in lipid metabolism, lysosomes, and the regulation of neurotransmission. Thus, concordance of proteomic and mRNA expression data within multiple categories validates the use of gene ontology analysis to compare different types of "omic" data. +AD - Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA C3 - Northwestern University C3 - Feinberg School of Medicine FU - NINDS NIH HHS [NS050641, NS046535] Funding Source: Medline +PU - AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC +PI - BETHESDA +PA - 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA +SN - 1535-9476 +SN - 1535-9484 +J9 - MOL CELL PROTEOMICS +JI - Mol. Cell. Proteomics +DA - JUL +PY - 2006 +VL - 5 +IS - 7 +SP - 1233 +EP - 1244 +DO - 10.1074/mcp.M500431-MCP200 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000238674800006 +N1 - Times Cited in Web of Science Core Collection: 34 +Total Times Cited: 34 +Cited Reference Count: 72 +ER - + +TY - JOUR +AU - Roos, A +AU - Schmitt, LI +AU - Hansmann, C +AU - Hezel, S +AU - Salmanian, S +AU - Hentschel, A +AU - Meyer, N +AU - Marina, AD +AU - Kölbel, H +AU - Kleinschnitz, C +AU - Schara-Schmidt, U +AU - Leo, M +AU - Hagenacker, T +TI - Alteration of LARGE1 abundance in patients and a mouse model of 5q-associated spinal muscular atrophy +T2 - ACTA NEUROPATHOLOGICA +LA - English +KW - SMA +KW - Proteomics +KW - Spinal cord +KW - Skeletal muscle +KW - CSF +KW - Serum +KW - SHAM CONTROL +KW - NUSINERSEN +KW - IDENTIFICATION +KW - INJURY +AB - Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by recessive pathogenic variants affecting the survival of motor neuron (SMN1) gene (localized on 5q). In consequence, cells lack expression of the corresponding protein. This pathophysiological condition is clinically associated with motor neuron (MN) degeneration leading to severe muscular atrophy. Additionally, vulnerability of other cellular populations and tissues including skeletal muscle has been demonstrated. Although the therapeutic options for SMA have considerably changed, treatment responses may differ thus underlining the persistent need for validated biomarkers. To address this need and to identify novel marker proteins for SMA, we performed unbiased proteomic profiling on cerebrospinal fluid derived (CSF) from genetically proven SMA type 1-3 cases and afterwards performed ELISA studies on CSF and serum samples to validate the potential of a novel biomarker candidates in both body fluids. To further decipher the pathophysiological impact of this biomarker, immunofluorescence studies were carried out on spinal cord and skeletal muscle derived from a 5q-SMA mouse model. Proteomics revealed increase of LARGE1 in CSF derived from adult patients showing a clinical response upon treatment with nusinersen. Moreover, LARGE1 levels were validated in CSF samples of further SMA patients (type 1-3) by ELISA. These studies also unveiled a distinguishment between groups in improvement of motor skills: adult patients do present with lowered level per se at baseline visit while no elevation upon treatment in the pediatric cohort can be observed. ELISA-based studies of serum samples showed no changes in the pediatric cohort but unraveled elevated level in adult patients responding to future intervention with nusinersen, while non-responders did not show a significant increase. Additional immunofluorescence studies of LARGE1 in MN and skeletal muscle of a SMA type 3 mouse model revealed an increase of LARGE1 during disease progression. Our combined data unraveled LARGE1 as a protein dysregulated in serum and CSF of SMA-patients (and in MN and skeletal muscle of SMA mice) holding the potential to serve as a disease marker for SMA and enabling to differentiate between patients responding and non-responding to therapy with nusinersen. +AD - Univ Hosp Essen, Ctr Neuromuscular Disorders, Ctr Translat Neuroand Behav Sci C TNBS, Dept Pediat Neurol, Hufelandstr 55, D-45147 Essen, Germany AD - Univ Ottawa, Ottawa Hosp, Brain & Mind Res Inst, Dept Med,Div Neurol, Ottawa, ON, Canada AD - Univ Ottawa, Childrens Hosp, Eastern Ontario Res Inst, Ottawa, ON, Canada AD - Univ Hosp Essen, Ctr Translat Neuroand Behav Sci CTNBS, Dept Neurol, Hufelandstr 55, D-45147 Essen, Germany AD - Leibniz Inst Analyt Wissensch ISAS eV, Otto Hahn Str 6B, D-44227 Dortmund, Germany C3 - University of Duisburg Essen C3 - University of Ottawa C3 - Ottawa Hospital Research Institute C3 - University of Ottawa C3 - Children's Hospital of Eastern Ontario C3 - University of Duisburg Essen C3 - Dortmund University of Technology C3 - Leibniz Association C3 - Leibniz Institut fur Analytische Wissenschaften (ISAS) FU - Projekt DEAL; Myelin Repair Foundation and the European Regional Development Fund (ERDF); German Society for Muscular Diseases (DGM) +FX - Open Access funding enabled and organized by Projekt DEAL. This research was funded by the Myelin Repair Foundation and the European Regional Development Fund (ERDF; project NME-GPS) as well as the German Society for Muscular Diseases (DGM; grant to AR and USS). +PU - SPRINGER +PI - NEW YORK +PA - ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES +SN - 0001-6322 +SN - 1432-0533 +J9 - ACTA NEUROPATHOL +JI - Acta Neuropathol. +DA - JUN +PY - 2024 +VL - 147 +IS - 1 +C7 - 53 +DO - 10.1007/s00401-024-02709-x +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001181657400003 +N1 - Times Cited in Web of Science Core Collection: 1 +Total Times Cited: 1 +Cited Reference Count: 31 +ER - + +TY - JOUR +AU - Deng, HS +AU - Xu, LS +AU - Ni, HD +AU - Wang, TT +AU - Liu, MJ +AU - Yang, MX +AU - Shen, H +AU - Pan, H +AU - Yao, M +TI - Proteomic profiling reveals Arl6ip-1 as a candidate target in cancer-induced bone pain rat model after oxycodone treatment +T2 - NEUROSCIENCE LETTERS +LA - English +KW - Cancer-induced bone pain +KW - Proteomics +KW - Oxycodone +KW - ADP-ribosylation factor-like 6 binding factor 1 +KW - GLUTAMATE TRANSPORTER EAAC1 +KW - ACTIVATION +KW - LOCALIZATION +KW - CONTRIBUTES +KW - MODULATION +KW - MORPHINE +AB - Treatment of cancer-induced bone pain (CIBP) is challenging in clinics. Oxycodone is used to treat CIBP. However, the lack of understanding of the mechanism of CIBP limits the application of oxycodone. In this study, proteomic profiling of oxycodone-treated spinal dorsal cord of rats with CIBP was performed. Briefly, a total of 3519 proteins were identified in the Sham group; 3505 proteins in the CIBP group; and 3530 proteins in the CIBP-OXY treatment group. The 2-fold cut-off value was used as the differential protein standard for abundance reduction or increase (p < 0.05). Significant differences were found in the abundance of 16 proteins between Sham and CIBP group; 11 proteins in the CIBP group had increased abundance while 5 proteins had reduced abundance. Furthermore, fifteen proteins with differential abundance were identified between the CIBP group and the OXY group. Compared with the CIBP group, there were six increased abundances and nine reduced abundances in the OXY group. In addition, a reduced expression of ADP-ribosylation factor-like 6 binding factor 1 (Arl6ip-1), an endoplasmic reticulum protein that has an important role in cell conduction and material transport, was found in the CIBP group compared with the Sham group. Its expression increased after the administration of OXY. Proteomics results were further verified by Western-blot. Fluorescent staining revealed that Arl6ip-1 co-localized with spinal dorsal horn neurons, but not with astrocytes or microglia. Based on the observed results, we believe that Arl6ip-1 may be a potential drug target for OXY treatment of CIBP rats. +AD - Jinxing Univ, Affiliated Hosp 1, Dept Anesthesiol & Pain Med, Jiaxing 314001, Peoples R China AD - Jinxing Univ, Affiliated Hosp 1, Dept Intens Care Unit, Jiaxing 314001, Peoples R China AD - Jinxing Univ, Affiliated Hosp 1, Dept Cent Lab, Jiaxing 314001, Peoples R China FU - Natural Science Foundation of Zhejiang Province [LY17H090019, LQ19H090007, LY16H090016]; TCM Research Foundation of Zhejiang Province [2016ZA190]; Science and Technology Project of Jiaxing City [2017AY33008, 2017AY33020, 2016AY23033]; National Natural Science Foundation of China [81341035, 81171057]; Construction Project of Anesthesiology Discipline Special Disease Center in Zhejiang North Region [201524]; Construction Project of Key Laboratory of Nerve and Pain Medicine in Jiaxing City +FX - This study was supported by the Natural Science Foundation of Zhejiang Province (LY17H090019, LQ19H090007 and LY16H090016), TCM Research Foundation of Zhejiang Province (2016ZA190), Science and Technology Project of Jiaxing City (2017AY33008, 2017AY33020 and 2016AY23033), National Natural Science Foundation of China (81341035 and 81171057), the Construction Project of Anesthesiology Discipline Special Disease Center in Zhejiang North Region (201524), and the Construction Project of Key Laboratory of Nerve and Pain Medicine in Jiaxing City. +PU - ELSEVIER IRELAND LTD +PI - CLARE +PA - ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND +SN - 0304-3940 +SN - 1872-7972 +J9 - NEUROSCI LETT +JI - Neurosci. Lett. +DA - APR 23 +PY - 2019 +VL - 699 +SP - 151 +EP - 159 +DO - 10.1016/j.neulet.2019.01.045 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000465055200024 +N1 - Times Cited in Web of Science Core Collection: 3 +Total Times Cited: 3 +Cited Reference Count: 27 +ER - + +TY - JOUR +AU - Fiani, B +AU - Covarrubias, C +AU - Jarrah, R +TI - Bench to Bedside: Proteomic Biomarker Analysis of Cerebrospinal Fluid in Patients With Spondylomyelopathy +T2 - CUREUS JOURNAL OF MEDICAL SCIENCE +LA - English +KW - vitamin d-binding protein +KW - gelsolin +KW - creatine kinase b-type +KW - angiotensinogen +KW - pigment epithelium-derived factor +KW - prostaglandin-h2 d-isomerase +KW - apolipoprotein e +KW - clusterin +KW - spondylomyelopathy +KW - proteomics +KW - VITAMIN-D +KW - HOMEOSTASIS +KW - COMPLEMENT +KW - PROTEIN +KW - SPARC +AB - Establishing proteomic biomarkers is critical for characterizing disease pathophysiology, identifying genetic risk factors, and predicting clinical outcomes. However, diseases like cervical spondylomyelopathy have not been actively characterized for molecular significance, leading to questions regarding the pathology's molecular mechanisms. Namely, spondylomyelopathy is a degenerative spinal disease that leads to compression and neurologic deficits in the spinal cord. Analyzing a patient's cerebrospinal fluid (CSF) has been well-known for revealing biomarkers that are associated with diseases of the central nervous system. Therefore, in this review, we will formulate a proteomic profile of spondylomyelopathy through a molecular analysis of the CSF. The proteins found to be upregulated in the CSF include vitamin D-binding protein (VDBP), gelsolin, creatine kinase B-type (CK-BB), and angiotensinogen. Meanwhile, the proteins that were downregulated include pigment epithelium-derived factor (PEDF), prostaglandin-H2 D-isomerase (PGH2), apolipoprotein E (APOE), and clusterin. The cellular functions of these proteins are discussed, along with their relevance in manifesting spondylomyelopathy. However, further studies are warranted, as a lack of human studies is a major limiting factor. Nevertheless, based on the continued progression of the proteomic profile of spondylomyelopathy, new targets can be assessed as candidates for future therapeutic intervention. +AD - Desert Reg Med Ctr, Neurosurg, Palm Springs, CA 92262 USA AD - Univ Anahuac Queretaro, Sch Med, Santiago De Queretaro, Mexico AD - Univ Michigan, Neurol Surg, Flint, MI 48503 USA C3 - University of Michigan System C3 - University of Michigan C3 - University of Michigan Flint PU - SPRINGERNATURE +PI - LONDON +PA - CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND +SN - 2168-8184 +J9 - CUREUS J MED SCIENCE +JI - Cureus J Med Sci +DA - JUN 28 +PY - 2021 +VL - 13 +IS - 6 +C7 - e16003 +DO - 10.7759/cureus.16003 +WE - Emerging Sources Citation Index (ESCI) AN - WOS:000668295100026 +N1 - Times Cited in Web of Science Core Collection: 0 +Total Times Cited: 0 +Cited Reference Count: 39 +ER - + +TY - JOUR +AU - Du, YD +AU - Yang, LL +AU - Wang, XX +AU - Jiang, N +AU - Zhou, YT +AU - Chen, RB +AU - Li, HY +TI - Proteome Profiling of Experimental Autoimmune Encephalomyelitis Mouse Model and the Effect of a SUMO E1 Inhibitor +T2 - JOURNAL OF PROTEOME RESEARCH +LA - English +KW - experimental autoimmune encephalomyelitis(EAE) +KW - multiplesclerosis +KW - quantitative proteomic analysis +KW - SUMOylation +KW - MULTIPLE-SCLEROSIS +KW - SUMOYLATION +KW - UBC9 +AB - Multiple sclerosis (MS) is one of the most common neurodegenerative diseases, causing demyelination and inflammation in the central nervous system. The pathology of MS has been extensively studied using the experimental autoimmune encephalomyelitis (EAE) mouse model. However, the molecular mechanisms are still largely unclear and require further investigation. In this study, we carried out quantitative proteomic analysis of the brain and spinal cord tissues in mice induced with EAE using a data-independent acquisition strategy and identified 744 differentially regulated proteins in the brain and 741 in the spinal cord. The changed proteins were highly related with phagocytosis, lysosomal enzymes, inflammasome activation, complements, and synaptic loss processes. Moreover, gene set enrichment analysis revealed the elevation of the SUMOylation process in EAE with the increase of SUMOylation-related enzymes and modification targets. Furthermore, to test the possibility of treating MS by targeting SUMOylation, we explored the application of a selective SUMO E1 inhibitor, TAK-981. Intriguingly, TAK-981 suppressed the global SUMOylation level in the brain and significantly alleviated the symptoms of EAE in mice. Our findings contribute to a better understanding of MS pathology, reveal the important role of SUMOylation in disease progression, and demonstrate the potential of the SUMO E1 inhibitor as a novel treatment for MS. +AD - Tianjin Univ, Fac Med, Sch Pharmaceut Sci & Technol, Tianjin 300072, Peoples R China AD - Capital Med Univ, Xuanwu Hosp, Gen Surg Dept, Beijing 100053, Peoples R China C3 - Tianjin University C3 - Capital Medical University FU - National Natural Science Foundation of China [2023YFC3403000]; National Key Research and Development Program of China [22474087, 82271373]; Natural Science Foundation of China [22JCYBJC00550]; Tianjin Natural Science Foundation [7232075]; Beijing Municipal Natural Science Foundation [KM202110025019]; Science and Technology Project of Beijing Municipal Education Commission [2018000026833ZK78]; Top-notch Project for Outstanding Talents in Beijing [CITTCD201904093]; Youth Top Talent Project of Beijing Municipal Education Commission +FX - This work was supported by grants from the National Key Research and Development Program of China (2023YFC3403000), Natural Science Foundation of China (22474087 and 82271373), Tianjin Natural Science Foundation (22JCYBJC00550), Beijing Municipal Natural Science Foundation (No. 7232075), Science and Technology Project of Beijing Municipal Education Commission (KM202110025019), Top-notch Project for Outstanding Talents in Beijing (2018000026833ZK78), and Youth Top Talent Project of Beijing Municipal Education Commission (CIT&TCD201904093). +PU - AMER CHEMICAL SOC +PI - WASHINGTON +PA - 1155 16TH ST, NW, WASHINGTON, DC 20036 USA +SN - 1535-3893 +SN - 1535-3907 +J9 - J PROTEOME RES +JI - J. Proteome Res. +DA - NOV 21 +PY - 2024 +VL - 23 +IS - 12 +SP - 5312 +EP - 5325 +DO - 10.1021/acs.jproteome.4c00229 +C6 - NOV 2024 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001360619900001 +N1 - Times Cited in Web of Science Core Collection: 0 +Total Times Cited: 0 +Cited Reference Count: 70 +ER - + +TY - JOUR +AU - Barriola, S +AU - Delgado-García, LM +AU - Cartas-Cejudo, P +AU - Iñigo-Marco, I +AU - Fernández-Irigoyen, J +AU - Santamaría, E +AU - López-Mascaraque, L +TI - Orosomucoid-1 Arises as a Shared Altered Protein in Two Models of Multiple Sclerosis +T2 - NEUROSCIENCE +LA - English +KW - proteomic analysis +KW - central nervous system (CNS) +KW - glia +KW - Ingenuity Pathway Analysis +KW - cortex +KW - spinal cord (SC) +KW - ACUTE-PHASE PROTEIN +KW - EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS +KW - CUPRIZONE-INDUCED DEMYELINATION +KW - BRAIN-BARRIER PERMEABILITY +KW - ALPHA-1-ACID GLYCOPROTEIN +KW - MOUSE MODELS +KW - EXPRESSION +KW - MICROGLIA +KW - PATHOGENESIS +KW - GENES +AB - sclerosis (MS) is a complex autoimmune and neurodegenerative disorder that affects the central nervous system (CNS). It is characterized by a heterogeneous disease course involving demyelination and inflammation. In this study, we utilized two distinct animal models, cuprizone (CPZ)-induced demyelination and experimental autoimmune encephalomyelitis (EAE), to replicate various aspects of the disease. We aimed to investigate the differential CNS responses by examining the proteomic profiles of EAE mice during the peak disease (15 days post-induction) and cuprizone-fed mice during the acute phase (38 days). Specifically, we focused on two different regions of the CNS: the dorsal cortex (Cx) and the entire spinal cord (SC). Our findings revealed varied glial, synaptic, dendritic, mitochondrial, and inflammatory responses within these regions for each model. Notably, we identified a single protein, Orosomucoid-1 (Orm1), also known as Alpha-1-acid glycoprotein 1 (AGP1), that consistently exhibited alterations in both models and regions. This study provides insights into the similarities and differences in the responses of these regions in two distinct demyelinating models.(c) 2023 IBRO. Published by Elsevier Ltd. All rights reserved. +AD - CSIC, Dept Mol Cellular & Dev Neurobiol, Inst Cajal, Madrid 28002, Spain AD - Autonoma Madrid Univ, Cajal Inst, Program Neurosci, Madrid 28029, Spain AD - Univ Fed Sao Paulo UNIFESP, Dept Biochem, Lab Mol Neurobiol, BR-04039032 Sao Paulo, Brazil AD - Univ Publ Navarra UPNA, Hosp Univ Navarra HUN, Clin Neuroprote Unit, Prote Platform,IDISNA, Pamplona 31008, Spain AD - CSIC, Inst Cajal, Mol Cellular & Dev Neurobiol Dept, Avda Doctor Arce 37, Madrid 28002, Spain C3 - Consejo Superior de Investigaciones Cientificas (CSIC) C3 - CSIC - Instituto Cajal (IC) C3 - Consejo Superior de Investigaciones Cientificas (CSIC) C3 - CSIC - Instituto Cajal (IC) C3 - Universidade Federal de Sao Paulo (UNIFESP) C3 - Servicio Navarro de Salud - Osasunbidea C3 - Universidad Publica de Navarra C3 - Consejo Superior de Investigaciones Cientificas (CSIC) C3 - CSIC - Instituto Cajal (IC) FU - MCIN/AEI [PRE2020-093827]; Fundacion Ramon Areces [CIVP9A5928]; Sao Paulo Research Foundation FAPESP [2016/19084-8, 2019/09183-7]; International Society for Neurochemistry ISN - CAEN A1 +FX - This work was supported by the Spanish Research Grants: PRE2020-093827 funded by MCIN/AEI/10.1303 9/501100011033 and CIVP9A5928 funded by Fundacion Ramon Areces. LMDG was supported by the Sao Paulo Research Foundation FAPESP (Grant Nos. 2016/19084-8 and 2019/09183-7) and the International Society for Neurochemistry ISN - CAEN A1. +PU - PERGAMON-ELSEVIER SCIENCE LTD +PI - OXFORD +PA - THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND +SN - 0306-4522 +SN - 1873-7544 +J9 - NEUROSCIENCE +JI - Neuroscience +DA - DEC 15 +PY - 2023 +VL - 535 +SP - 203 +EP - 217 +DO - 10.1016/j.neuroscience.2023.10.015 +C6 - NOV 2023 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001118916100001 +N1 - Times Cited in Web of Science Core Collection: 0 +Total Times Cited: 0 +Cited Reference Count: 91 +ER - + +TY - JOUR +AU - Komori, M +AU - Matsuyama, Y +AU - Nirasawa, T +AU - Thiele, H +AU - Becker, M +AU - Alexandrov, T +AU - Saida, T +AU - Tanaka, M +AU - Matsuo, H +AU - Tomimoto, H +AU - Takahashi, R +AU - Tashiro, K +AU - Ikegawa, M +AU - Kondo, T +TI - Proteomic pattern analysis discriminates among multiple sclerosis-related disorders +T2 - ANNALS OF NEUROLOGY +LA - English +KW - CEREBROSPINAL-FLUID PROTEOME +KW - SPINAL-CORD LESIONS +KW - NEUROMYELITIS-OPTICA +KW - MASS-SPECTROMETRY +KW - ANTI-AQUAPORIN-4 ANTIBODY +KW - DIAGNOSTIC-CRITERIA +KW - CSF BIOMARKERS +KW - IDENTIFICATION +KW - MARKER +KW - SPECTRUM +AB - Objective: To use a new, unbiased biomarker discovery strategy to obtain and assess proteomic data from cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS)-related disorders. Methods: CSF protein profiles were analyzed from 107 patients with either MS-related disorders (including relapsing remitting MS [RRMS], primary progressive MS [PPMS], anti-aquaporin4 antibody seropositive-neuromyelitis optica spectrum disorder [SP-NMOSD], and seronegative-NMOSD with long cord lesions on spinal magnetic resonance imaging [SN-NMOSD]), amyotrophic lateral sclerosis (ALS), or other inflammatory neurological diseases (used as controls). CSF peptides/ proteins were purified with magnetic beads, and directly measured by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry. The obtained spectra were analyzed with multivariate statistics and pattern matching algorithms. These analyses were replicated in an independent sample set of 84 patients composed of those with MS-related disorders or with other neurological diseases (the second cohort). Results: MS-related disorders differed considerably in terms of CSF protein profiles. SP-NMOSD and SN-NMOSD, both of which fit within the NMO spectrum, were distinguishable from RRMS with high cross-validation accuracy on a support vector machine classifier, especially in relapse phases. Some peaks derived from samples of relapsed SPNMOSD can discriminate RRMS with high area under curve scores (> 0.95) and this was reproduced on the second cohort. The similarity of proteomic patterns between selected neurological diseases were demonstrated by pattern matching analysis. To our surprise, the spectral differences between RRMS and PPMS were much larger than those of PPMS and ALS. Interpretation: Our findings suggest that CSF proteomic pattern analysis can increase the accuracy of disease diagnosis of MS-related disorders and will aid physicians in appropriate therapeutic decision-making. ANN NEUROL 2012; 71: 614-623 +AD - Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Genom Med Sci, Kamigyo Ku, Kyoto 6028566, Japan AD - Kitano Hosp, Tazuke Kofukai Med Res Inst, Osaka, Japan AD - Kyoto Univ, Grad Sch Med, Dept Neurol, Kyoto, Japan AD - Bruker Dalton KK, Yokohama, Kanagawa, Japan AD - Bruker Daltonik GmbH, Bremen, Germany AD - Univ Bremen, Ctr Ind Math, D-28359 Bremen, Germany AD - Natl Utano Hosp, Dept Neurol, Kyoto, Japan AD - Nagasaki Med Ctr Neurol, Div Clin Res, Nagasaki, Japan C3 - Kyoto Prefectural University of Medicine C3 - Kitano Hospital C3 - Kyoto University C3 - Bruker Corporation C3 - Bruker Daltonik GmbH C3 - University of Bremen FU - Grants-in-Aid for Scientific Research [22390325, 23659160] Funding Source: KAKEN +PU - WILEY-BLACKWELL +PI - MALDEN +PA - COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA +SN - 0364-5134 +J9 - ANN NEUROL +JI - Ann. Neurol. +DA - MAY +PY - 2012 +VL - 71 +IS - 5 +SP - 614 +EP - 623 +DO - 10.1002/ana.22633 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000303040700006 +N1 - Times Cited in Web of Science Core Collection: 21 +Total Times Cited: 25 +Cited Reference Count: 35 +ER - + +TY - JOUR +AU - Liu, C +AU - Lin, MTY +AU - Lee, IXY +AU - Wong, JHF +AU - Lu, DQ +AU - Lam, TC +AU - Zhou, L +AU - Mehta, JS +AU - Ong, HS +AU - Ang, M +AU - Tong, LI +AU - Liu, YC +TI - Neuropathic Corneal Pain: Tear Proteomic and Neuromediator Profiles, Imaging Features, and Clinical Manifestations +T2 - AMERICAN JOURNAL OF OPHTHALMOLOGY +LA - English +KW - VIVO CONFOCAL MICROSCOPY +KW - GROWTH-FACTOR +KW - SPINAL-CORD +KW - MECHANICAL ALLODYNIA +KW - OCULAR PAIN +KW - DRY EYE +KW - NERVE +KW - HYPERSENSITIVITY +KW - DENERVATION +KW - RELIABILITY +AB - center dot PURPOSE: To investigate the tear proteomic and neuromediator profiles, in vivo confocal microscopy (IVCM) imaging features, and clinical manifestations in neuropathic corneal pain (NCP) patients. center dot DESIGN: Cross-sectional study. center dot METHODS: A total of 20 NCP patients and 20 agematched controls were recruited. All subjects were evaluated by corneal sensitivity, Schirmer test, tear break-up time, and corneal and ocular surface staining, Ocular Surface Disease Index and Ocular Pain Assessment Survey questionnaires were administered, as well as IVCM examinations for corneal nerves, microneruomas, and epithelial and dendritic cells. Tears were collected for neuromediator and proteomic analysis using enzyme-linked immunosorbent assay and data-independent acquisition mass spectrometry. center dot RESULTS: Burning and sensitivity to light were the 2 most common symptoms in NCP. A total of 188 significantly dysregulated proteins, such as elevated metallothionein-2, creatine kinases B-type, vesicleassociated membrane protein 2, neurofilament light polypeptide, and myelin basic protein, were identified in the NCP patients. The top 10 dysregulated biological pathways in NCP include neurotoxicity, axonal signaling, wound healing, neutrophil degradation, apoptosis, thrombin signaling mitochondrial dysfunction, and RHOGDI and P70S6K signaling pathways. Compared to controls, the NCP cohort presented with significantly decreased corneal sensitivity ( P < .001), decreased corneal nerve fiber length ( P = .003), corneal nerve fiber density ( P = .006), and nerve fiber fractal dimension ( P = .033), as well as increased corneal nerve fiber width ( P = .002), increased length, total area and perimeter of microneuromas ( P < .001, P < .001, P = .019), smaller corneal epithelial size ( P = .017), and higher nerve growth factor level in tears ( P = .006). center dot CONCLUSIONS: These clinical manifestations, imaging features, and molecular characterizations would contribute to the diagnostics and potential therapeutic targets for NCP. (Am J Ophthalmol 2024;265: 6-20. (c) 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )) +AD - Singapore Eye Res Inst, Tissue Engn & Cell Therapy Grp, Singapore, Singapore AD - Singapore Eye Res Inst, Cornea & Refract Surg Grp, Singapore, Singapore AD - Singapore Eye Res Inst, Clin Res Platform, Singapore, Singapore AD - Hong Kong Polytech Univ, Ctr Myopia Res, Sch Optometry, Hong Kong, Peoples R China AD - Ctr Eye & Vis Res CEVR, Hong Kong, Peoples R China AD - Res Ctr SHARP Vis RCSV, Sch Optometry, Dept Appl Biol & Chem Technol, Hong Kong, Peoples R China AD - Hong Kong Polytech Univ, Sch Optometry, Ctr Myopia Res, Hong Kong, Peoples R China AD - Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore AD - Singapore Eye Res Inst, Ocular Surface Res Grp, Singapore, Singapore AD - Duke NUS Med Sch, Eye Acad Clin Program, Singapore, Singapore C3 - Singapore National Eye Center C3 - National University of Singapore C3 - Singapore National Eye Center C3 - National University of Singapore C3 - Singapore National Eye Center C3 - National University of Singapore C3 - Hong Kong Polytechnic University C3 - Hong Kong Polytechnic University C3 - National University of Singapore C3 - Singapore National Eye Center C3 - National University of Singapore C3 - National University of Singapore FU - Clinician Scientist Award Grant from the Singapore National Medical Research Council [MOH- CSAINV21jun-0001] +FX - The study is supported by the Clinician Scientist Award Grant from the Singapore National Medical Research Council (MOH- CSAINV21jun-0001) . +PU - ELSEVIER SCIENCE INC +PI - NEW YORK +PA - STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA +SN - 0002-9394 +SN - 1879-1891 +J9 - AM J OPHTHALMOL +JI - Am. J. Ophthalmol. +DA - SEP +PY - 2024 +VL - 265 +SP - 6 +EP - 20 +DO - 10.1016/j.ajo.2024.03.015 +C6 - MAY 2024 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001240659400001 +N1 - Times Cited in Web of Science Core Collection: 1 +Total Times Cited: 1 +Cited Reference Count: 77 +ER - + +TY - JOUR +AU - Tokuyama, S +TI - RETRACTION: Proteomic Profiling in the Spinal Cord and Sciatic Nerve in a Global Cerebral Ischemia-Induced Mechanical Allodynia Mouse Model (Retraction of Vol 39, Pg 230, 2016) +T2 - BIOLOGICAL & PHARMACEUTICAL BULLETIN +LA - English +AD - Kobe Gakuin Univ, Dept Clin Pharm, Sch Pharmaceut Sci, Kobe, Hyogo, Japan C3 - Kobe Gakuin University PU - PHARMACEUTICAL SOC JAPAN +PI - TOKYO +PA - 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN +SN - 0918-6158 +SN - 1347-5215 +J9 - BIOL PHARM BULL +JI - Biol. Pharm. Bull. +DA - NOV +PY - 2019 +VL - 42 +IS - 11 +SP - 1957 +EP - 1957 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000494055400027 +N1 - Times Cited in Web of Science Core Collection: 0 +Total Times Cited: 0 +Cited Reference Count: 1 +ER - + +TY - JOUR +AU - Stella, R +AU - Bonadio, RS +AU - Cagnin, S +AU - Massimino, ML +AU - Bertoli, A +AU - Peggion, C +TI - Perturbations of the Proteome and of Secreted Metabolites in Primary Astrocytes from the hSOD1(G93A) ALS Mouse Model +T2 - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES +LA - English +KW - spinal cord astrocytes +KW - ALS +KW - glutathione metabolism +KW - proteolysis +KW - metabolomics +KW - proteomics +KW - transcription factors +KW - AMYOTROPHIC-LATERAL-SCLEROSIS +KW - MOTOR-NEURON DEGENERATION +KW - TRANSGENIC MICE +KW - OXIDATIVE STRESS +KW - NERVOUS-SYSTEM +KW - IN-VITRO +KW - GENE +KW - EXPRESSION +KW - GLUTAMATE +KW - DISEASE +AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease whose pathophysiology is largely unknown. Despite the fact that motor neuron (MN) death is recognized as the key event in ALS, astrocytes dysfunctionalities and neuroinflammation were demonstrated to accompany and probably even drive MN loss. Nevertheless, the mechanisms priming astrocyte failure and hyperactivation are still obscure. In this work, altered pathways and molecules in ALS astrocytes were unveiled by investigating the proteomic profile and the secreted metabolome of primary spinal cord astrocytes derived from transgenic ALS mouse model overexpressing the human (h)SOD1(G93A) protein in comparison with the transgenic counterpart expressing hSOD1(WT) protein. Here we show that ALS primary astrocytes are depleted of proteins-and of secreted metabolites-involved in glutathione metabolism and signaling. The observed increased activation of Nf-kB, Ebf1, and Plag1 transcription factors may account for the augmented expression of proteins involved in the proteolytic routes mediated by proteasome or endosome-lysosome systems. Moreover, hSOD1(G93A) primary astrocytes also display altered lipid metabolism. Our results provide novel insights into the altered molecular pathways that may underlie astrocyte dysfunctionalities and altered astrocyte-MN crosstalk in ALS, representing potential therapeutic targets to abrogate or slow down MN demise in disease pathogenesis. +AD - Ist Zooprofilatt Sperimentale Venezie, Dept Chem, I-35020 Legnaro, Italy AD - Univ Padua, Dept Biol, I-35131 Padua, Italy AD - Univ Padua, CRIBI Biotechnol Ctr, I-35131 Padua, Italy AD - Univ Padua, CIR Myo Myol Ctr, I-35131 Padua, Italy AD - CNR, Neurosci Inst, I-35131 Padua, Italy AD - Univ Padua, Padova Neurosci Ctr, I-35131 Padua, Italy AD - Univ Padua, Dept Biomed Sci, I-35131 Padua, Italy C3 - IZS delle Venezie C3 - University of Padua C3 - University of Padua C3 - University of Padua C3 - Consiglio Nazionale delle Ricerche (CNR) C3 - University of Padua C3 - University of Padua FU - University of Padova [BIRD202151/20] +FX - This work was supported by grants from University of Padova (BIRD202151/20) to A.B. +PU - MDPI +PI - BASEL +PA - ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND +SN - 1422-0067 +J9 - INT J MOL SCI +JI - Int. J. Mol. Sci. +DA - JUL +PY - 2021 +VL - 22 +IS - 13 +C7 - 7028 +DO - 10.3390/ijms22137028 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000671128000001 +N1 - Times Cited in Web of Science Core Collection: 10 +Total Times Cited: 10 +Cited Reference Count: 103 +ER - + +TY - JOUR +AU - Levine, J +AU - Kwon, E +AU - Paez, P +AU - Yan, WH +AU - Czerwieniec, G +AU - Loo, JA +AU - Sofroniew, MV +AU - Wanner, IB +TI - Traumatically injured astrocytes release a proteomic signature modulated by STAT3-dependent cell survival +T2 - GLIA +LA - English +KW - trauma +KW - proteome +KW - astrocyte +KW - mechanoporation +KW - biomarker +KW - FIBRILLARY ACIDIC PROTEIN +KW - SPINAL-CORD-INJURY +KW - ALPHA-B-CRYSTALLIN +KW - STRETCH-INDUCED INJURY +KW - IN-VITRO TRAUMA +KW - BRAIN-INJURY +KW - WHITE-MATTER +KW - CULTURED ASTROCYTES +KW - CEREBROSPINAL-FLUID +KW - CEREBRAL CONTUSION +AB - Molecular markers associated with CNS injury are of diagnostic interest. Mechanical trauma generates cellular deformation associated with membrane permeability with unknown molecular consequences. We used an in vitro model of stretch-injury and proteomic analyses to determine protein changes in murine astrocytes and their surrounding fluids. Abrupt pressure-pulse stretching resulted in the rapid release of 59 astrocytic proteins with profiles reflecting cell injury and cell death, i.e., mechanoporation and cell lysis. This acute trauma-release proteome was overrepresented with metabolic proteins compared with the uninjured cellular proteome, bearing relevance for post-traumatic metabolic depression. Astrocyte-specific deletion of signal transducer and activator of transcription 3 (STAT3-CKO) resulted in reduced stretch-injury tolerance, elevated necrosis and increased protein release. Consistent with more lysed cells, more protein complexes, nuclear and transport proteins were released from STAT3-CKO versus nontransgenic astrocytes. STAT3-CKO astrocytes had reduced basal expression of GFAP, lactate dehydrogenase B (LDHB), aldolase C (ALDOC), and astrocytic phosphoprotein 15 (PEA15), and elevated levels of tropomyosin (TPM4) and actinin 4 (ACTN4). Stretching caused STAT3-dependent cellular depletion of PEA15 and GFAP, and its filament disassembly in subpopulations of injured astrocytes. PEA15 and ALDOC signals were low in injured astrocytes acutely after mouse spinal cord crush injury and were robustly expressed in reactive astrocytes 1 day postinjury. In contrast, crystallin (CRYAB) was present in acutely injured astrocytes, and absent from uninjured and reactive astrocytes, demonstrating novel marker differences among postinjury astrocytes. These findings reveal a proteomic signature of traumatically-injured astrocytes reflecting STAT3-dependent cellular survival with potential diagnostic value. GLIA 2016;64:668-694 +AD - Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, David Geffen Sch Med, Los Angeles, CA 90095 USA AD - SUNY Buffalo, Dept Pharmacol & Toxicol, Hunter James Kelly Res Inst, Sch Med & Biomed Sci,NYS Ctr Excellence, Buffalo, NY 14260 USA AD - Univ Calif Los Angeles, Dept Chem & Biochem, 405 Hilgard Ave, Los Angeles, CA 90024 USA AD - Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA AD - Univ Calif Los Angeles, UCLA DOE Inst Genom & Proteom, Los Angeles, CA USA AD - Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA C3 - University of California System C3 - University of California Los Angeles C3 - University of California Los Angeles Medical Center C3 - David Geffen School of Medicine at UCLA C3 - State University of New York (SUNY) System C3 - University at Buffalo, SUNY C3 - University of California System C3 - University of California Los Angeles C3 - University of California System C3 - University of California Los Angeles C3 - University of California Los Angeles Medical Center C3 - David Geffen School of Medicine at UCLA C3 - United States Department of Energy (DOE) C3 - University of California System C3 - University of California Los Angeles C3 - University of California System C3 - University of California Los Angeles C3 - University of California Los Angeles Medical Center C3 - David Geffen School of Medicine at UCLA FU - NIH [1R21NS072606, R01NS057624, R01GM104610]; Craig H. Neilsen Foundation [82776]; Dr. Miriam and Sheldon Adelson Medical Research Foundation +FX - Grant sponsor: NIH; Grant number: 1R21NS072606 to IBW; R01NS057624 to MVS; and R01GM104610 to JAL; Grant sponsor: Craig H. Neilsen Foundation (82776 to IBW).; Grant sponsor: Dr. Miriam and Sheldon Adelson Medical Research Foundation (to MVS). +PU - WILEY-BLACKWELL +PI - HOBOKEN +PA - 111 RIVER ST, HOBOKEN 07030-5774, NJ USA +SN - 0894-1491 +SN - 1098-1136 +J9 - GLIA +JI - Glia +DA - MAY +PY - 2016 +VL - 64 +IS - 5 +SP - 668 +EP - 694 +DO - 10.1002/glia.22953 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000373197000002 +N1 - Times Cited in Web of Science Core Collection: 51 +Total Times Cited: 55 +Cited Reference Count: 91 +ER - + +TY - JOUR +AU - Ma, JJ +AU - Lin, ZG +AU - Zhang, YQ +AU - Ding, Y +AU - Tang, QM +AU - Qian, YF +AU - Jin, B +AU - Luo, RY +AU - Liao, WL +AU - Thyparambil, S +AU - Han, Z +AU - Chou, CJ +AU - Schilling, J +AU - Li, Q +AU - Zhang, MX +AU - Lin, YN +AU - Ma, Y +AU - Sylvester, KG +AU - Nagpal, S +AU - McElhinney, DB +AU - Ling, XB +AU - Chen, BB +TI - Targeted multiplex validation of CSF proteomic biomarkers: implications for differentiation of PCNSL from tumor-free controls and other brain tumors +T2 - FRONTIERS IN IMMUNOLOGY +LA - English +KW - primary central nervous system lymphoma (PCNSL) +KW - diffuse large B-cell lymphoma (DLBCL) +KW - cerebrospinal fluid (CSF) +KW - targeted proteomics +KW - liquid chromatography tandem-mass spectrometry (LC-MS/MS) +KW - NERVOUS-SYSTEM LYMPHOMA +KW - PRIMARY CNS LYMPHOMA +KW - CEREBROSPINAL-FLUID +KW - DIAGNOSIS +KW - SURVIVAL +KW - PATHWAY +KW - LEVEL +AB - Introduction Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation.Methods CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels.Results Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features.Discussion This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes. +AD - Fudan Univ, Huashan Hosp, Dept Hematol, Shanghai, Peoples R China AD - Guangdong Polytech Normal Univ, Coll Automat, Guangzhou, Peoples R China AD - mProbe Inc, Res & Dev, Palo Alto, CA USA AD - Stanford Univ, Sch Med, Dept Pathol, Stanford, CA USA AD - Stanford Univ, Sch Med, Dept Biomed Data Sci, Stanford, CA USA AD - Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA AD - Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, Stanford, CA USA AD - Stanford Univ, Dept Cardiothorac Surg, Sch Med, Stanford, CA USA AD - Stanford Univ, Dept Pediat Cardiol, Sch Med, Stanford, CA USA C3 - Fudan University C3 - Guangdong Polytechnic Normal University C3 - Stanford University C3 - Stanford University C3 - Stanford University C3 - Stanford University C3 - Stanford University C3 - Stanford University FU - Shanghai Shenkang Clinical Innovation Project - Shanghai Municipal Health Commission Health Industry Clinical Research Project [SHDC12020112]; [20214Y0107] +FX - The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study is part of a research project (SHDC12020112) that was funded by Shanghai Shenkang Clinical Innovation Project. This study was also funded by Shanghai Municipal Health Commission Health Industry Clinical Research Project (20214Y0107). +PU - FRONTIERS MEDIA SA +PI - LAUSANNE +PA - AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND +SN - 1664-3224 +J9 - FRONT IMMUNOL +JI - Front. Immunol. +DA - AUG 1 +PY - 2024 +VL - 15 +C7 - 1343109 +DO - 10.3389/fimmu.2024.1343109 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001290194500001 +N1 - Times Cited in Web of Science Core Collection: 0 +Total Times Cited: 0 +Cited Reference Count: 37 +ER - + +TY - JOUR +AU - Varderidou-Minasian, S +AU - Verheijen, BM +AU - Harschnitz, O +AU - Kling, S +AU - Karst, H +AU - van der Pol, WL +AU - Pasterkamp, RJ +AU - Altelaar, M +TI - Spinal Muscular Atrophy Patient iPSC-Derived Motor Neurons Display Altered Proteomes at Early Stages of Differentiation +T2 - ACS OMEGA +LA - English +KW - DETERMINING GENE-PRODUCT +KW - PLURIPOTENT STEM-CELLS +KW - MESSENGER-RNA +KW - SMN PROTEIN +KW - SINGLE NUCLEOTIDE +KW - MOUSE MODELS +KW - SURVIVAL +KW - DEFICIENCY +KW - COMPLEX +KW - IDENTIFICATION +AB - Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder characterized by loss of motor neurons (MN) in the spinal cord leading to progressive muscle atrophy and weakness. SMA is caused by mutations in the survival motor neuron 1 (SMN1) gene, resulting in reduced levels of survival motor neuron (SMN) protein. The mechanisms that link SMN deficiency to selective motor neuron dysfunction in SMA remain largely unknown. We present here, for the first time, a comprehensive quantitative TMT-10plex proteomics analysis that covers the development of induced pluripotent stem cell-derived MNs from both healthy individuals and SMA patients. We show that the proteomes of SMA samples segregate from controls already at early stages of neuronal differentiation. The altered proteomic signature in SMA MNs is associated with mRNA splicing, ribonucleoprotein biogenesis, organelle organization, cellular biogenesis, and metabolic processes. We highlight several known SMN-binding partners and evaluate their expression changes during MN differentiation. In addition, we compared our study to human and mouse in vivo proteomic studies revealing distinct and similar signatures. Altogether, our work provides a comprehensive resource of molecular events during early stages of MN differentiation, containing potentially therapeutically interesting protein expression profiles for SMA. +AD - Univ Utrecht, Univ Med Ctr Utrecht, UMC Utrecht Brain Ctr, Dept Translat Neurosci, NL-3584 CG Utrecht, Netherlands AD - Univ Utrecht, Univ Med Ctr Utrecht, UMC Utrecht Brain Ctr, Dept Neurol & Neurosurg, NL-3584 CX Utrecht, Netherlands AD - Univ Utrecht, Biomol Mass Spectrometry & Prote, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands AD - Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CH Utrecht, Netherlands AD - Netherlands Prote Ctr, NL-3584 CH Utrecht, Netherlands AD - Univ Southern Calif, Los Angeles, CA 90007 USA AD - Sloan Kettering Inst Canc Res, Ctr Stem Cell Biol, New York, NY USA AD - Sloan Kettering Inst Canc Res, Dev Biol Program, New York, NY USA AD - Univ Med Ctr Utrecht, Ctr Mol Med, Univ Weg 100, NL-3584 CG Utrecht, Netherlands C3 - Utrecht University C3 - Utrecht University Medical Center C3 - Utrecht University C3 - Utrecht University Medical Center C3 - Utrecht University C3 - Utrecht University C3 - University of Southern California C3 - Memorial Sloan Kettering Cancer Center C3 - Memorial Sloan Kettering Cancer Center C3 - Utrecht University C3 - Utrecht University Medical Center FU - Netherlands Organization for Scientific Research (NWO) [723.012.102]; Proteins@Work, a program of the National Roadmap Large-Scale Research Facilities of the Netherlands [184.032.201]; Dutch ALS foundation; Spieren voor Spieren +FX - This work was supported by the Netherlands Organization for Scientific Research (NWO) through a VIDI grant for M.A. (723.012.102) and Proteins@Work, a program of the National Roadmap Large-Scale Research Facilities of the Netherlands (project number 184.032.201). We thank Dr. Vivi M. Heine (VU University, Amsterdam, the Netherlands) for providing control fibroblasts. We thank the UMC Utrecht MIND facility and Ms. Danielle Vonk for help with iPSC work and Dutch ALS foundation grants "TOTALS" and "ALS-on-a-chip" for funding (to R.J.P.) and Spieren voor Spieren (to W.L.v.d.P.). +PU - AMER CHEMICAL SOC +PI - WASHINGTON +PA - 1155 16TH ST, NW, WASHINGTON, DC 20036 USA +SN - 2470-1343 +J9 - ACS OMEGA +JI - ACS Omega +DA - DEC 28 +PY - 2021 +VL - 6 +IS - 51 +SP - 35375 +EP - 35388 +DO - 10.1021/acsomega.1c04688 +C6 - DEC 2021 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000733820900001 +N1 - Times Cited in Web of Science Core Collection: 9 +Total Times Cited: 9 +Cited Reference Count: 77 +ER - + +TY - JOUR +AU - Park, S +AU - Lee, J +TI - Proteomic analysis to identify early molecular targets of pregabalin in C6 glial cells +T2 - CELL BIOLOGY INTERNATIONAL +LA - English +KW - C6 glial cell +KW - calreticulin +KW - cytoskeleton +KW - DJ-1 +KW - pregabalin +KW - proteomic approach +KW - SPINAL-CORD +KW - ENDOPLASMIC-RETICULUM +KW - PRECOLUMN DERIVATIZATION +KW - OXIDATIVE STRESS +KW - GABAPENTIN +KW - DJ-1 +KW - PAIN +KW - RAT +KW - CALRETICULIN +KW - MODEL +AB - Pregabalin is a lipophilic amino acid derivative of gamma-amino butyric acid that displays anticonvulsant and analgesic activities against neuropathic pain. Although a role for glial cells as an important player in pain control and also as a new target for pain medicine has been suggested, the effect of pregabalin on glial cells has not been elucidated. In the present study, we have investigated the action of pregabalin on the glial cell proteome. To identify immediate early protein targets of pregabalin in glial cells, a differential proteomics approach in C6 rat glioma cells treated with pregabalin was used. Seven proteins that sensitively reacted to pregabalin treatment were identified using two-dimensional gel electrophoresis and MALDI-TOF-MS (matrix-assisted laser-desorption ionization time-of-flight MS). The calcium-ion-binding chaperone, calreticulin, and the oxidative response protein, DJ-1, were up-regulated after pregabalin treatment. Hsp (heat-shock protein)-90-beta, cytoskeleton protein actin and myosin also showed quantitative expression profile differences. Functionally relevant to the proteome result, immediate actin depolymerization was observed after treatment with pregabalin. These results suggest a previously undefined role of pregabalin in the regulation of chaperone activity and cytoskeleton remodelling in glial cells. +AD - Dongduk Womens Univ, Dept Appl Chem, Seoul 136714, South Korea AD - Yonsei Univ, Dept Food & Nutr, Seoul 134, South Korea C3 - Dongduk Women's University C3 - Yonsei University FU - Korean Government [R01-2008-000-10470-0, 2008-0058300, 2009-0058300] +FX - This work was supported by the KOSEF (Korea Science and Engineering Foundation) grant funded by the Korean Government [grant numbers R01-2008-000-10470-0, 2008-0058300, 2009-0058300 (Programme for Basic Science)]. +PU - WILEY +PI - HOBOKEN +PA - 111 RIVER ST, HOBOKEN 07030-5774, NJ USA +SN - 1065-6995 +SN - 1095-8355 +J9 - CELL BIOL INT +JI - Cell Biol. Int. +DA - JAN +PY - 2010 +VL - 34 +IS - 1 +SP - 27 +EP - 33 +DO - 10.1042/CBI20090018 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000277391400005 +N1 - Times Cited in Web of Science Core Collection: 6 +Total Times Cited: 7 +Cited Reference Count: 44 +ER - + +TY - JOUR +AU - Pierre, S +AU - Maeurer, C +AU - Coste, O +AU - Becker, W +AU - Schmidtko, A +AU - Holland, S +AU - Wittpoth, C +AU - Geisslinger, G +AU - Scholich, K +TI - Toponomics Analysis of Functional Interactions of the Ubiquitin Ligase PAM (Protein Associated with Myc) during Spinal Nociceptive Processing +T2 - MOLECULAR & CELLULAR PROTEOMICS +LA - English +KW - 2ND MESSENGER SYSTEM +KW - D-ASPARTATE RECEPTOR +KW - INFLAMMATORY PAIN +KW - SYNAPTIC GROWTH +KW - C-ELEGANS +KW - GLUTAMATE RECEPTORS +KW - PROTEOMIC ANALYSIS +KW - ADENYLYL CYCLASES +KW - MICE LACKING +KW - SENSITIZATION +AB - Protein associated with Myc (PAM) is a giant E3 ubiquitin ligase of 510 kDa. Although the role of PAM during neuronal development is well established, very little is known about its function in the regulation of synaptic strength. Here we used multiepitope ligand cartography (MELC) to study protein network profiles associated with PAM during the modulation of synaptic strength. MELC is a novel imaging technology that utilizes biomathematical tools to describe protein networks after consecutive immunohistochemical visualization of up to 100 proteins on the same sample. As an in vivo model to modulate synaptic strength we used the formalin test, a common model for acute and inflammatory pain. MELC analysis was performed with 37 different antibodies or fluorescence tags on spinal cord slices and led to the identification of 1390 PAM-related motifs that distinguish untreated and formalin-treated spinal cords. The majority of these motifs related to ubiquitin-dependent processes and/or the actin cytoskeleton. We detected an intermittent colocalization of PAM and ubiquitin with TSC2, a known substrate of PAM, and the glutamate receptors mGluR5 and GLUR1. Importantly these complexes were detected exclusively in the presence of F-actin. A direct PAM/F-actin interaction was confirmed by colocalization and cosedimentation. The binding of PAM toward F-actin varied strongly between the PAM splice forms found in rat spinal cords. PAM did not ubiquitylate actin or alter actin polymerization and depolymerization. However, F-actin decreased the ubiquitin ligase activity of purified PAM. Because PAM activation is known to involve its translocation, the binding of PAM to F-actin may serve to control its subcellular localization as well as its activity. Taken together we show that defining protein network profiles by topological proteomics analysis is a useful tool to identify previously unknown protein/protein interactions that underlie synaptic processes. Molecular & Cellular Proteomics 7:2475-2485, 2008. +AD - Univ Frankfurt, Inst Klin Pharmakol, Pharmazentrum Frankfurt, ZAFES, D-60590 Frankfurt, Germany AD - MeITec GmbH, D-39120 Magdeburg, Germany C3 - Goethe University Frankfurt FU - Deutsche Forschungsgemeinschaft [SCHO817-1, SCHO817-2] +FX - The work was supported by Deutsche Forschungsgemeinschaft Grants SCHO817-1 and -2. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. +PU - AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC +PI - BETHESDA +PA - 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA +SN - 1535-9476 +J9 - MOL CELL PROTEOMICS +JI - Mol. Cell. Proteomics +DA - DEC +PY - 2008 +VL - 7 +IS - 12 +SP - 2475 +EP - 2485 +DO - 10.1074/mcp.M800201-MCP200 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000261328200016 +N1 - Times Cited in Web of Science Core Collection: 28 +Total Times Cited: 31 +Cited Reference Count: 47 +ER - + +TY - JOUR +AU - Glanzer, JG +AU - Enose, Y +AU - Wang, T +AU - Kadiu, I +AU - Gong, N +AU - Rozek, W +AU - Liu, JN +AU - Schlautman, JD +AU - Ciborowski, PS +AU - Thomas, MP +AU - Gendelman, HE +TI - Genomic and proteomic microglial profiling: pathways for neuroprotective inflammatory responses following nerve fragment clearance and activation +T2 - JOURNAL OF NEUROCHEMISTRY +LA - English +KW - cathepsins +KW - microglia +KW - neurotrophins +KW - NF kappa B +KW - optic nerve +KW - proteomics +KW - SPINAL-CORD-INJURY +KW - ACQUIRED-IMMUNODEFICIENCY-SYNDROME +KW - CILIARY NEUROTROPHIC FACTOR +KW - HUMAN CATHEPSIN-B +KW - GROWTH-FACTOR +KW - OPTIC-NERVE +KW - MYELIN PHAGOCYTOSIS +KW - MONONUCLEAR PHAGOCYTES +KW - LIQUID-CHROMATOGRAPHY +KW - MURINE MACROPHAGES +AB - Microglia, a primary immune effector cell of the central nervous system (CNS) affects homeostatic, neuroprotective, regenerative and degenerative outcomes in health and disease. Despite these broad neuroimmune activities linked to specific environmental cues, a precise cellular genetic profile for microglia in the context of disease and repair has not been elucidated. To this end we used nucleic acid microarrays, proteomics, immunochemical and histochemical tests to profile microglia in neuroprotective immune responses. Optic and sciatic nerve (ON and SN) fragments were used to stimulate microglia in order to reflect immune consequences of nervous system injury. Lipopolysaccharide and latex beads-induced microglial activation served as positive controls. Cytosolic and secreted proteins were profiled by surface enhanced laser desorption ionization-time of flight (SELDI-TOF) ProteinChip (R) 1 D and 2D difference gel electrophoresis. Proteins were identified by peptide sequencing with tandem mass spectrometry, ELISA and western blot tests. Temporal expression of pro-inflammatory cytokines, antioxiclants, neurotrophins, and lysosomal enzyme expression provided, for the first time, a unique profile of secreted microglia proteins with neuroregulatory functions. Most importantly, this molecular and biochemical signature supports a broad range of microglial functions for debris clearance and promotion of neural repair after injury. +AD - Univ Nebraska, Med Ctr, Ctr Neurovirol & Neurodegenerat Disorders, Nebraska Med Ctr, Omaha, NE 68198 USA AD - Univ Nebraska, Med Ctr, Dept Pharmacol, Omaha, NE 68198 USA AD - Univ Nebraska, Med Ctr, Dept Expt Neurosci, Omaha, NE 68198 USA AD - Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE 68198 USA AD - Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA AD - Natl Vet Inst, Dept Virol, Pulawy, Poland C3 - University of Nebraska System C3 - University of Nebraska Medical Center C3 - University of Nebraska System C3 - University of Nebraska Medical Center C3 - University of Nebraska System C3 - University of Nebraska Medical Center C3 - University of Nebraska System C3 - University of Nebraska Medical Center C3 - University of Nebraska System C3 - University of Nebraska Medical Center C3 - National Veterinary Institute - National Research Institute FU - NCRR NIH HHS [P20 RR15635] Funding Source: Medline; NIMH NIH HHS [R21 MH075662] Funding Source: Medline; NINDS NIH HHS [P01 NS31492, P01 NS43985, 5 F32 NS046894, 2 R01 NS034239, U54 NS43011-01, 2R37 NS36126] Funding Source: Medline +PU - WILEY +PI - HOBOKEN +PA - 111 RIVER ST, HOBOKEN 07030-5774, NJ USA +SN - 0022-3042 +SN - 1471-4159 +J9 - J NEUROCHEM +JI - J. Neurochem. +DA - AUG +PY - 2007 +VL - 102 +IS - 3 +SP - 627 +EP - 645 +DO - 10.1111/j.1471-4159.2007.04568.x +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000248504200006 +N1 - Times Cited in Web of Science Core Collection: 59 +Total Times Cited: 67 +Cited Reference Count: 71 +ER - + +TY - JOUR +AU - Li, WT +AU - Sun, HL +AU - Xu, ZL +AU - Ding, F +AU - Gu, XS +TI - Protein expression profile in the differentiation of rat bone marrow stromal cells into Schwann cell-like cells +T2 - SCIENCE IN CHINA SERIES C-LIFE SCIENCES +LA - English +KW - one marrow stromal cells (MSCs) +KW - differentiation +KW - Schwann cell-like cells +KW - proteomics +KW - MESENCHYMAL STEM-CELLS +KW - CILIARY NEUROTROPHIC FACTOR +KW - SPINAL-CORD-INJURY +KW - ADULT-RAT +KW - IN-VITRO +KW - NEURONAL DIFFERENTIATION +KW - MOTONEURON SURVIVAL +KW - FUNCTIONAL RECOVERY +KW - PROTEOMIC ANALYSIS +KW - ISCHEMIC BRAIN +AB - During the last decade, increasing evidence suggested that bone marrow stromal cells (MSCs) have the potential to differentiate into neural lineages. Many studies have reported that MSCs showed morphological changes and expressed a limited number of neural proteins under experimental conditions. However, no proteomic studies on MSCs differentiated into Schwann cell-like cells have been reported. In this study, we isolated MSCs from adult Sprague-Dawley rat femur and tibia bone marrows and induced the cells in vitro under specific conditions. By using two-dimensional gel electrophoresis (2-DE), we compared the protein profiles of MSCs before and after induced differentiation. We obtained 792 protein spots in the protein profile by 2-DE, and found that 74 spots changed significantly before and after the differentiation using PDQuest software, with 43 up-regulated and 31 down-regulated. We analyzed these 74 spots by a matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) and by database searching, and found that they could be grouped into various classes, including cytoskeleton and structure proteins, growth factors, metabolic proteins, chaperone proteins, receptor proteins, cell cycle proteins, calcium binding proteins, and other proteins. These proteins also include neural and glial proteins, such as BDNF, CNTF and GFAP. The results may provide valuable proteomic information about the differentiation of MSCs into Schwann cell-like cells. +AD - Nantong Univ, Jiangsu Key Lab Neuroregenerat, Nantong 226001, Peoples R China AD - Chinese Acad Med Sci, Dept Anat Histol & Embryol, Peking Union Med Coll, Inst Basic Med Sci, Beijing 100005, Peoples R China C3 - Nantong University C3 - Institute of Basic Medical Sciences - CAMS C3 - Chinese Academy of Medical Sciences - Peking Union Medical College C3 - Peking Union Medical College FU - National High-Tech Research and Development Program of China [2006AA02A128]; National Natural Science Foundation of China [30670667] +FX - Supported by National High-Tech Research and Development Program of China (Grant No. 2006AA02A128) and National Natural Science Foundation of China (Grant No. 30670667). +PU - SCIENCE PRESS +PI - BEIJING +PA - 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA +SN - 1006-9305 +J9 - SCI CHINA SER C +JI - Sci. China Ser. C-Life Sci. +DA - MAR +PY - 2009 +VL - 52 +IS - 3 +SP - 267 +EP - 277 +DO - 10.1007/s11427-009-0033-4 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000264329900010 +N1 - Times Cited in Web of Science Core Collection: 2 +Total Times Cited: 3 +Cited Reference Count: 50 +ER - + +TY - JOUR +AU - Echevarria-Lima, J +AU - Pereira, DD +AU - De Oliveira, TS +AU - Espindola, OD +AU - Lima, MA +AU - Leite, ACC +AU - Sandim, V +AU - Nascimento, CR +AU - Kalume, DE +AU - Zingali, RB +TI - Protein Profile of Blood Monocytes is Altered in HTLV-1 Infected Patients: Implications for HAM/TSP Disease +T2 - SCIENTIFIC REPORTS +LA - English +KW - T-CELL LEUKEMIA +KW - VIRUS TYPE-I +KW - MYELOPATHY/TROPICAL SPASTIC PARAPARESIS +KW - DENDRITIC CELLS +KW - MONONUCLEAR-CELLS +KW - GENE-EXPRESSION +KW - TYPE-1 +KW - GELSOLIN +KW - SUBSETS +KW - DIFFERENTIATION +AB - Human T-cell lymphotropic virus type-1 (HTLV-1) is the etiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The endothelial breakdown and migration of leukocytes, including monocytes, to the spinal cord are involved in HAM/TSP development. Monocytes from HTLV-1-infected individuals exhibit important functional differences when compared to cells from uninfected donors. Using proteomic shot gun strategy, performed by nanoACQUITY-UPLC system, we analyzed monocytes isolated from peripheral blood of asymptomatic carriers (AC), HAM/TSP and uninfected individuals. 534 proteins were identified among which 376 were quantified by Expression(E) software. Our study revealed a panel of changes in protein expression linked to HTLV-1 infection. Upregulation of heat shock proteins and downregulation of canonical histone expression were observed in monocytes from HTLV-1-infected patients. Moreover, expression of cytoskeleton proteins was increased in monocytes from HTLV-1-infected patients, mainly in those from HAM/TSP, which was confirmed by flow cytometry and fluorescence microscopy. Importantly, functional assays demonstrated that monocytes from HAM/TSP patients present higher ability for adhesion and transmigration thought endothelium than those from AC and uninfected individuals. The major changes on monocyte protein profile were detected in HAM/TSP patients, suggesting that these alterations exert a relevant role in the establishment of HAM/TSP. +AD - Univ Fed Rio de Janeiro, Lab Imunol Basica & Aplicada, Dept Immunol, Inst Microbiol Paulo Goes, Rio de Janeiro, RJ, Brazil AD - Univ Fed Rio de Janeiro, UEMP, Inst Bioquim Med Leopoldo Meis, Rio de Janeiro, RJ, Brazil AD - Univ Fed Rio de Janeiro, INBEB, Rio de Janeiro, RJ, Brazil AD - Inst Nacl Canc, Programa Oncobiol Celular & Mol, Coordenacao Geral Ensino & Pesquisa, Rio De Janeiro, RJ, Brazil AD - Fundacao Oswaldo Cruz, FIOCRUZ, Lab Pesquisa Clin Neuroinfeccoes, Inst Nacl Infectol Evandro Chagas INI, Rio De Janeiro, RJ, Brazil AD - Univ Fed Rio de Janeiro, IBCCF, Lab Imunol Mol, Rio de Janeiro, Brazil AD - Fundacao Oswaldo Cruz, FIOCRUZ, IOC, Lab Interdisciplinar Pesquisas Med, Rio De Janeiro, RJ, Brazil C3 - Universidade Federal do Rio de Janeiro C3 - Universidade Federal do Rio de Janeiro C3 - Universidade Federal do Rio de Janeiro C3 - National Cancer Institute (Inca) C3 - Fundacao Oswaldo Cruz C3 - Universidade Federal do Rio de Janeiro C3 - Fundacao Oswaldo Cruz FU - Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ); Fundacao Oswaldo Cruz; Brazilian Ministry of Health; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Institutional Scientific Initiation Scholarship Program UFRJ/CNPq; Fundacao do Cancer +FX - We are thankful for the Mass Spectrometry and Proteomics Unit core facility (UEMP) at Rio de Janeiro Federal University run by Russolina B. Zingali for supporting in using SYNAPT HDMS system and bioinformatics analyses. We thank Grasiela Ventura for her help with image acquisition. This work was supported by grants from Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundacao Oswaldo Cruz, and Brazilian Ministry of Health, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq). Clarissa Rodrigues Nascimento was the recipient of a Postdoc Research Fellowship from FAPERJ, Thais Oliveira was the recipient of a fellowship from Institutional Scientific Initiation Scholarship Program UFRJ/CNPq, and Vanessa Sandim is recipient of a FAPERJ Postdoc research fellowship and received a postdoctoral fellowship from Fundacao do Cancer. +PU - NATURE PORTFOLIO +PI - BERLIN +PA - HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY +SN - 2045-2322 +J9 - SCI REP-UK +JI - Sci Rep +DA - SEP 25 +PY - 2018 +VL - 8 +C7 - 14354 +DO - 10.1038/s41598-018-32324-2 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000445572100013 +N1 - Times Cited in Web of Science Core Collection: 3 +Total Times Cited: 3 +Cited Reference Count: 58 +ER - + +TY - JOUR +AU - Chmelova, M +AU - Androvic, P +AU - Kirdajova, D +AU - Tureckova, J +AU - Kriska, J +AU - Valihrach, L +AU - Anderova, M +AU - Vargova, L +TI - A view of the genetic and proteomic profile of extracellular matrix molecules in aging and stroke +T2 - FRONTIERS IN CELLULAR NEUROSCIENCE +LA - English +KW - extracellular matrix +KW - stroke +KW - aging +KW - genes +KW - proteins +KW - CHONDROITIN SULFATE PROTEOGLYCANS +KW - FOCAL CEREBRAL-ISCHEMIA +KW - CENTRAL-NERVOUS-SYSTEM +KW - UBIQUITIN-PROTEASOME SYSTEM +KW - LINK PROTEIN +KW - RAT-BRAIN +KW - PERINEURONAL NETS +KW - SPINAL-CORD +KW - REACTIVE ASTROCYTES +KW - ARTERY OCCLUSION +AB - IntroductionModification of the extracellular matrix (ECM) is one of the major processes in the pathology of brain damage following an ischemic stroke. However, our understanding of how age-related ECM alterations may affect stroke pathophysiology and its outcome is still very limited.MethodsWe conducted an ECM-targeted re-analysis of our previously obtained RNA-Seq dataset of aging, ischemic stroke and their interactions in young adult (3-month-old) and aged (18-month-old) mice. The permanent middle cerebral artery occlusion (pMCAo) in rodents was used as a model of ischemic stroke. Altogether 56 genes of interest were chosen for this study.ResultsWe identified an increased activation of the genes encoding proteins related to ECM degradation, such as matrix metalloproteinases (MMPs), proteases of a disintegrin and metalloproteinase with the thrombospondin motifs (ADAMTS) family and molecules that regulate their activity, tissue inhibitors of metalloproteinases (TIMPs). Moreover, significant upregulation was also detected in the mRNA of other ECM molecules, such as proteoglycans, syndecans and link proteins. Notably, we identified 8 genes where this upregulation was enhanced in aged mice in comparison with the young ones. Ischemia evoked a significant downregulation in only 6 of our genes of interest, including those encoding proteins associated with the protective function of ECM molecules (e.g., brevican, Hapln4, Sparcl1); downregulation in brevican was more prominent in aged mice. The study was expanded by proteome analysis, where we observed an ischemia-induced overexpression in three proteins, which are associated with neuroinflammation (fibronectin and vitronectin) and neurodegeneration (link protein Hapln2). In fibronectin and Hapln2, this overexpression was more pronounced in aged post-ischemic animals.ConclusionBased on these results, we can conclude that the ratio between the protecting and degrading mechanisms in the aged brain is shifted toward degradation and contributes to the aged tissues' increased sensitivity to ischemic insults. Altogether, our data provide fresh perspectives on the processes underlying ischemic injury in the aging brain and serve as a freely accessible resource for upcoming research. +AD - Charles Univ Prague, Fac Med 2, Dept Neurosci, Prague, Czech Republic AD - Czech Acad Sci, Inst Expt Med, Dept Cellular Neurophysiol, Prague, Czech Republic AD - Czech Acad Sci BIOCEV, Inst Biotechnol, Lab Gene Express, Vestec, Czech Republic C3 - Motol University Hospital C3 - Charles University Prague C3 - Czech Academy of Sciences C3 - Institute of Experimental Medicine of the Czech Academy of Sciences C3 - Czech Academy of Sciences C3 - Institute of Biotechnology of the Czech Academy of Sciences FU - Czech Science Foundation [21-24674S, 23-06269S]; Czech Academy of Sciences [L200392251]; [RVO 86652036] +FX - The authors declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants 21-24674S and 23-06269S from the Czech Science Foundation (MA), L200392251 from the Czech Academy of Sciences (JK), and by the Institutional support RVO 86652036. +PU - FRONTIERS MEDIA SA +PI - LAUSANNE +PA - AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND +SN - 1662-5102 +J9 - FRONT CELL NEUROSCI +JI - Front. Cell. Neurosci. +DA - NOV 30 +PY - 2023 +VL - 17 +C7 - 1296455 +DO - 10.3389/fncel.2023.1296455 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001126829000001 +N1 - Times Cited in Web of Science Core Collection: 1 +Total Times Cited: 1 +Cited Reference Count: 158 +ER - + +TY - JOUR +AU - Caldwell, RL +AU - Opalenik, SR +AU - Davidson, JM +AU - Caprioli, RM +AU - Nanney, LB +TI - Tissue profiling MALDI mass spectrometry reveals prominent calcium-binding proteins in the proteome of regenerative MRL mouse wounds +T2 - WOUND REPAIR AND REGENERATION +LA - English +KW - SPINAL-CORD TRANSECTION +KW - GENE-EXPRESSION +KW - ADULT RATS +KW - S100A4 +KW - INJURY +KW - SKIN +KW - MIGRATION +KW - DISEASE +KW - CELLS +KW - LASER +AB - MRL/MpJ-Fas(lpr) mice exhibit the ability to regenerate ear tissue excised by dermal punches. This is an exceptional model to identify candidate proteins that may regulate regeneration in typically nonregenerative tissues. Identification of key molecules involved in regeneration can broaden our understanding of the wound-healing process and generate novel therapeutic approaches. Tissue profiling by matrix-assisted laser desorption ionization mass spectrometry is a rapid, powerful proteomic tool that allows hundreds of proteins to be detected from specific regions of intact tissue specimens. To identify these candidate molecules, protein expression in ear punches was examined after 4 and 7 days using tissue profiling of MRL/MpJ-Fas(lpr) mice and the nonregenerative mouse strain C57BL/6J. Spectral analysis revealed distinct proteomic differences between the regenerative and nonregenerative phenotypes, including the calcium-binding proteins calgranulin A and B, calgizzarin, and calmodulin. Spatial distributions for these differentially expressed proteins within the injured regions were confirmed by immunohistochemistry. +AD - Vanderbilt Univ, Med Ctr, Dept Plast Surg, Sch Med, Nashville, TN 37232 USA AD - VA TVHS Med Ctr, Med Res Serv, Nashville, TN 37232 USA AD - Vanderbilt Univ, Sch Med, Vanderbilt Orthopaed Inst, Nashville, TN 37232 USA AD - Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA AD - Vanderbilt Univ, Sch Med, Mass Spectrometry Res Ctr, Nashville, TN 37232 USA AD - Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA C3 - Vanderbilt University C3 - US Department of Veterans Affairs C3 - Veterans Health Administration (VHA) C3 - VA Tennessee Valley Healthcare System C3 - Vanderbilt University C3 - Vanderbilt University C3 - Vanderbilt University C3 - Vanderbilt University FU - NIAMS NIH HHS [P30 AR041943-148493, P30 AR41943, P30 AR041943] Funding Source: Medline; NIA NIH HHS [R01 AG006528, R01 AG006528-18S1, AG06528] Funding Source: Medline; NIGMS NIH HHS [R01 GM058008-08, R01 GM058008, R01 GM040437, GM40437, 5R01 GM 58008, R01 GM040437-17] Funding Source: Medline +PU - WILEY +PI - HOBOKEN +PA - 111 RIVER ST, HOBOKEN 07030-5774, NJ USA +SN - 1067-1927 +SN - 1524-475X +J9 - WOUND REPAIR REGEN +JI - Wound Repair Regen. +DA - MAY-JUN +PY - 2008 +VL - 16 +IS - 3 +SP - 442 +EP - 449 +DO - 10.1111/j.1524-475X.2007.00351.x +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000255666500015 +N1 - Times Cited in Web of Science Core Collection: 27 +Total Times Cited: 36 +Cited Reference Count: 45 +ER - + +TY - JOUR +AU - Saydam, O +AU - Senol, O +AU - Schaaij-Visser, TBM +AU - Pham, TV +AU - Piersma, SR +AU - Stemmer-Rachamimov, AO +AU - Wurdinger, T +AU - Peerdeman, SM +AU - Jimenez, CR +TI - Comparative Protein Profiling Reveals Minichromosome Maintenance (MCM) Proteins As Novel Potential Tumor Markers for Meningiomas +T2 - JOURNAL OF PROTEOME RESEARCH +LA - English +KW - meningiomas +KW - proteomics +KW - tumor markers +KW - MCMs +KW - PROGESTERONE-RECEPTOR EXPRESSION +KW - DNA-REPLICATION +KW - STATISTICAL-MODEL +KW - GENETIC MODEL +KW - CANCER +KW - NF2 +KW - PROGRESSION +KW - RECURRENCE +KW - BENIGN +KW - MIB-1 +AB - Meningiomas are among the most frequent tumors of the brain and spinal cord accounting for 15-20% of all central nervous system tumors and frequently associated with neurofibromatosis type 2. In this study, we aimed to unravel molecular meningioma tumorigenesis and discover novel protein biomarkers for diagnostic and/or prognostic purposes and performed in-depth proteomic profiling of meningioma cells compared to human primary arachnoidal cells. We isolated proteins from meningioma cell line SF4433 and human primary arachnoidal cells and analyzed the protein profiles by Gel-nanoLC-MS/MS in conjunction with protein identification and quantification by shotgun nanoLC tandem mass spectrometry and spectral counting. Differential analysis of meningiomas revealed changes in the expression levels of 281 proteins (P < 0.01) associated with various biological functions such as DNA replication, recombination, cell cycle, and apoptosis. Among several interesting proteins, we focused on a subset of the highly significantly up-regulated proteins, the minichromosome maintenance (MCM) family. We performed subsequent validation studies by qRT-PCR in human meningioma tissue samples (WHO grade I, 14 samples; WHO grade II, 7 samples; and WHO grade III, 7 samples) compared to arachnoidal tissue controls (from fresh autopsies; 3 samples) and found that MCMs are highly and significantly up-regulated in human meningioma tumor samples compared to arachnoidal tissue controls. We found a significant increase in MCM2 (8 fold), MCM3 (5 fold), MCM4 (4 fold), MCM5 (4 fold), MCM6 (3 fold), and MCM7 (5 fold) expressions in meningiomas. This study suggests that MCM family proteins are up-regulated in meningiomas and can be used as diagnostic markers. +AD - Vrije Univ Amsterdam Med Ctr, OncoProte Lab, Dept Med Oncol, VUmc Canc Ctr Amsterdam, Amsterdam, Netherlands AD - Harvard Univ, Dept Neurol, Sch Med, Boston, MA 02129 USA AD - Harvard Univ, Dept Radiol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA AD - Harvard Univ, Neurosci Program, Sch Med, Boston, MA 02129 USA AD - Harvard Univ, Mol Neurooncol Lab, Sch Med, Boston, MA 02129 USA AD - Harvard Univ, Dept Pathol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA AD - Vrije Univ Amsterdam Med Ctr, Neurooncol Res Grp, Amsterdam, Netherlands AD - Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Amsterdam, Netherlands C3 - Vrije Universiteit Amsterdam C3 - VU UNIVERSITY MEDICAL CENTER C3 - Harvard University C3 - Harvard Medical School C3 - Harvard University C3 - Harvard Medical School C3 - Massachusetts General Hospital C3 - Harvard University C3 - Harvard Medical School C3 - Harvard University C3 - Harvard Medical School C3 - Harvard University C3 - Harvard Medical School C3 - Massachusetts General Hospital C3 - Vrije Universiteit Amsterdam C3 - VU UNIVERSITY MEDICAL CENTER C3 - Vrije Universiteit Amsterdam C3 - VU UNIVERSITY MEDICAL CENTER FU - Children's Tumor Foundation [2007-01-043]; NINDS [NS24279]; VUmc-Cancer Center Amsterdam +FX - This study was supported by the Children's Tumor Foundation 2007-01-043 (O.S.) and NINDS NS24279 (O.S.). We thank Ms. Silvina A. Fratantoni for assistance with the SDS-PAGE and in-gel digestion of the samples, Marianne F. James for human primary arachnoidal cells (Massachusetts General Hospital), and Dr. Xandra O. Breakefield for providing laboratory facilities for this work. The VUmc-Cancer Center Amsterdam is acknowledged for financial support for the proteornics infrastructure (T.V.P. and C.R.J.). +PU - AMER CHEMICAL SOC +PI - WASHINGTON +PA - 1155 16TH ST, NW, WASHINGTON, DC 20036 USA +SN - 1535-3893 +SN - 1535-3907 +J9 - J PROTEOME RES +JI - J. Proteome Res. +DA - JAN +PY - 2010 +VL - 9 +IS - 1 +SP - 485 +EP - 494 +DO - 10.1021/pr900834h +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000273267900046 +N1 - Times Cited in Web of Science Core Collection: 53 +Total Times Cited: 62 +Cited Reference Count: 58 +ER - + +TY - JOUR +AU - Rosenling, T +AU - Stoop, MP +AU - Attali, A +AU - van Aken, H +AU - Suidgeest, E +AU - Christin, C +AU - Stingl, C +AU - Suits, F +AU - Horvatovich, P +AU - Hintzen, RQ +AU - Tuinstra, T +AU - Bischoff, R +AU - Luider, TM +TI - Profiling and Identification of Cerebrospinal Fluid Proteins in a Rat EAE Model of Multiple Sclerosis +T2 - JOURNAL OF PROTEOME RESEARCH +LA - English +KW - proteomics +KW - experimental autoimmune encephalomyelitis +KW - multiple sclerosis +KW - cerebrospinal fluid +KW - QTOF peptide profiling +KW - Orbitrap peptide profiling +KW - EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS +KW - EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS +KW - BLOOD-BRAIN-BARRIER +KW - SPINAL-CORD +KW - VITAMIN-D +KW - OXIDATIVE STRESS +KW - PROTEOMICS ANALYSIS +KW - MASS-SPECTROMETRY +KW - DISEASE-ACTIVITY +KW - EXPRESSION +AB - The experimental autoimmune encephalomyelitis (EAR) model resembles certain aspects of multiple sclerosis (MScl), with common features such as motor dysfunction, axonal degradation, and infiltration of T-cells. We studied the cerebrospinal fluid (CSF) proteome in the EAE rat model to identify proteomic changes relevant for MSd disease pathology. EAE was induced in male Lewis rats by injection of myelin basic protein (MBP) together with complete Freund's adjuvant (CFA). An inflammatory control group was injected with CFA alone, and a nontreated group served as healthy control. CSF was collected at day 10 and 14 after immunization and analyzed by bottom-up proteomics on Orbitrap LC-MS and QTOF LC-MS platforms in two independent laboratories. By combining results, 44 proteins were discovered to be significantly increased in EAE animals compared to both control groups, 25 of which have not been mentioned in relation to the EAE model before. Lysozyme Cl, fetuin B, T-kininogen, serum paraoxonase/arylesterase 1, glutathione peroxidase 3, complement C3, and afamin are among the proteins significantly elevated in this rat EAE model. Two proteins, afamin and complement C3, were validated in an independent sample set using quantitative selected reaction monitoring mass spectrometry. The molecular weights of the identified differentially abundant proteins indicated an increased transport across the blood brain barrier (BBB) at the peak of the disease, caused by an increase in BBB permeability. +AD - Erasmus Univ, Dept Neurol, Med Ctr, Rotterdam, Netherlands AD - Univ Groningen, Dept Analyt Biochem, Ctr Pharm, Groningen, Netherlands AD - Abbott Healthcare Prod BV, Weesp, Netherlands AD - IBM Corp, TJ Watson Res Ctr, Yorktown Hts, NY USA C3 - Erasmus University Rotterdam C3 - Erasmus MC C3 - University of Groningen C3 - International Business Machines (IBM) C3 - IBM USA FU - Top Institute Pharma [D4-102]; Netherlands Proteomics [BioRange 2.2.3]; Netherlands Bioinformatics Center; Dutch Multiple Sclerosis Foundation +FX - This study was performed within the framework of Top Institute Pharma project D4-102. The work was also supported by the project BioRange 2.2.3 from The Netherlands Proteomics and The Netherlands Bioinformatics Center as well as by the Dutch Multiple Sclerosis Foundation. We thank Balaji Srinivasan (University of Groningen) for preparation of the CSF samples for chipLC-QTOF analysis. +PU - AMER CHEMICAL SOC +PI - WASHINGTON +PA - 1155 16TH ST, NW, WASHINGTON, DC 20036 USA +SN - 1535-3893 +J9 - J PROTEOME RES +JI - J. Proteome Res. +DA - APR +PY - 2012 +VL - 11 +IS - 4 +SP - 2048 +EP - 2060 +DO - 10.1021/pr201244t +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000302388100004 +N1 - Times Cited in Web of Science Core Collection: 46 +Total Times Cited: 48 +Cited Reference Count: 83 +ER - + +TY - JOUR +AU - Cervenka, J +AU - Tylecková, J +AU - Skalníková, HK +AU - Kepková, KV +AU - Poliakh, I +AU - Valeková, I +AU - Pfeiferová, L +AU - Kolár, M +AU - Vaskovicová, M +AU - Panková, T +AU - Vodicka, P +TI - Proteomic Characterization of Human Neural Stem Cells and Their Secretome During in vitro Differentiation +T2 - FRONTIERS IN CELLULAR NEUROSCIENCE +LA - English +KW - neural stem cell +KW - proliferation +KW - neural differentiation +KW - secretome +KW - proteome +KW - VEGF +KW - SWATH-MS +KW - ENDOTHELIAL GROWTH-FACTOR +KW - DOPAMINERGIC-NEURONS +KW - SIGNALING PATHWAYS +KW - PROGENITOR CELLS +KW - ISCHEMIC BRAIN +KW - FACTOR VEGF +KW - R PACKAGE +KW - EXPRESSION +KW - GENE +KW - TRANSPLANTATION +AB - Cell therapies represent a promising approach to slow down the progression of currently untreatable neurodegenerative diseases (e.g., Alzheimer's and Parkinson's disease or amyotrophic lateral sclerosis), as well as to support the reconstruction of functional neural circuits after spinal cord injuries. In such therapies, the grafted cells could either functionally integrate into the damaged tissue, partially replacing dead or damaged cells, modulate inflammatory reaction, reduce tissue damage, or support neuronal survival by secretion of cytokines, growth, and trophic factors. Comprehensive characterization of cells and their proliferative potential, differentiation status, and population purity before transplantation is crucial to preventing safety risks, e.g., a tumorous growth due to the proliferation of undifferentiated stem cells. We characterized changes in the proteome and secretome of human neural stem cells (NSCs) during their spontaneous (EGF/FGF2 withdrawal) differentiation and differentiation with trophic support by BDNF/GDNF supplementation. We used LC-MS/MS in SWATH-MS mode for global cellular proteome profiling and quantified almost three thousand cellular proteins. Our analysis identified substantial protein differences in the early stages of NSC differentiation with more than a third of all the proteins regulated (including known neuronal and NSC multipotency markers) and revealed that the BDNF/GDNF support affected more the later stages of the NSC differentiation. Among the pathways identified as activated during both spontaneous and BDNF/GDNF differentiation were the HIF-1 signaling pathway, Wnt signaling pathway, and VEGF signaling pathway. Our follow-up secretome analysis using Luminex multiplex immunoassay revealed significant changes in the secretion of VEGF and IL-6 during NSC differentiation. Our results further demonstrated an increased expression of neuropilin-1 as well as catenin beta-1, both known to participate in the regulation of VEGF signaling, and showed that VEGF-A isoform 121 (VEGF121), in particular, induces proliferation and supports survival of differentiating cells. +AD - Czech Acad Sci, Inst Anim Physiol & Genet, Res Ctr PIGMOD, Lab Appl Proteome Anal, Libechov, Czech Republic AD - Charles Univ Prague, Fac Sci, Dept Cell Biol, Prague, Czech Republic AD - Czech Acad Sci, Inst Anim Physiol & Genet, Lab Cell Regenerat & Plast, Res Ctr PIGMOD, Libechov, Czech Republic AD - Czech Acad Sci, Inst Mol Genet, Lab Genom & Bioinformat, Prague, Czech Republic AD - Univ Chem & Technol, Dept Informat & Chem, Fac Chem Technol, Prague, Czech Republic AD - Czech Acad Sci, Inst Anim Physiol & Genet, Res Ctr PIGMOD, Lab DNA Integr, Libechov, Czech Republic C3 - Czech Academy of Sciences C3 - Institute of Animal Physiology & Genetics of the Czech Academy of Sciences C3 - Charles University Prague C3 - Czech Academy of Sciences C3 - Institute of Animal Physiology & Genetics of the Czech Academy of Sciences C3 - Czech Academy of Sciences C3 - Institute of Molecular Genetics of the Czech Academy of Sciences C3 - University of Chemistry & Technology, Prague C3 - Czech Academy of Sciences C3 - Institute of Animal Physiology & Genetics of the Czech Academy of Sciences FU - Czech Ministry of Education, Youth and Sports [LTC18079, CA16119]; National Sustainability Programme I [LO1609]; Operational Programme Research, Development and Education [CZ.02.1.01/0.0/0.0/16_019/0000785]; Charles University project GA UK [1767518] +FX - This research was supported by the Czech Ministry of Education, Youth and Sports projects InterCOST (LTC18079) under CellFit COST Action (CA16119), National Sustainability Programme I (LO1609), Operational Programme Research, Development and Education (CZ.02.1.01/0.0/0.0/16_019/0000785), and Charles University project GA UK (1767518). +PU - FRONTIERS MEDIA SA +PI - LAUSANNE +PA - AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND +SN - 1662-5102 +J9 - FRONT CELL NEUROSCI +JI - Front. Cell. Neurosci. +DA - JAN 28 +PY - 2021 +VL - 14 +C7 - 612560 +DO - 10.3389/fncel.2020.612560 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000616808200001 +N1 - Times Cited in Web of Science Core Collection: 26 +Total Times Cited: 27 +Cited Reference Count: 93 +ER - + +TY - JOUR +AU - Liu, YS +AU - Teng, XH +AU - Yang, XX +AU - Song, Q +AU - Lu, R +AU - Xiong, JX +AU - Liu, B +AU - Zeng, NJ +AU - Zeng, Y +AU - Long, J +AU - Cao, R +AU - Lin, Y +AU - He, QZ +AU - Chen, P +AU - Lu, M +AU - Liang, SP +TI - Shotgun Proteomics and Network Analysis Between Plasma Membrane and Extracellular Matrix Proteins From Rat Olfactory Ensheathing Cells +T2 - CELL TRANSPLANTATION +LA - English +KW - Olfactory ensheathing cells +KW - Neural repair +KW - 1D-shotgun proteomics +KW - Plasma membrane +KW - Extracellular matrix +KW - CENTRAL-NERVOUS-SYSTEM +KW - APOLIPOPROTEIN-E-GENOTYPE +KW - SPINAL-CORD INJURIES +KW - GROWTH-FACTOR +KW - BINDING PROTEIN-2 +KW - SIGNAL PEPTIDES +KW - GENE ONTOLOGY +KW - SCHWANN-CELLS +KW - STEM-CELLS +KW - IN-VITRO +AB - Olfactory ensheathing cells (OECs) are a special type of dial cells that have characteristics of both astrocytes and Schwann cells. Evidence suggests that the regenerative capacity of OECs is induced by soluble, secreted factors that influence their microenvironment These factors may regulate OECs self-renewal and/or induce their capacity to augment spinal cord regeneration Profiling of plasma membrane and extracellular matrix through a high-throughput expression proteomics approach was undertaken to identify plasma membrane and extracellular matrix proteins of OECs under serum-free conditions 1D-shotgun proteomics followed with gene ontology (GO) analysis was used to screen proteins from primary culture rat OECs Four hundred and seventy nonredundant plasma membrane proteins and 168 extracellular matrix proteins were identified, the majority of which were never before reported to be produced by OECs Furthermore. plasma membrane and extracellular proteins were classified based on their protein protein interaction predicted by STRING quantitatively integrates interaction data The proteomic profiling of the OECs plasma membrane proteins and their connection with the secretome in serum-free culture conditions provides new insights into the nature of their in vivo microenvironmental niche Proteomic analysis for the discovery of clinical biomarkers of OECs mechanism warrants further study +AD - Hunan Normal Univ, Key Lab Prot Chem & Dev Biol, Minist Educ, Coll Life Sci, Changsha 410081, Hunan, Peoples R China AD - Hunan Normal Univ, Hosp PLA 163, Affiliated Hosp 2, Dept Neurosurg, Changsha 410081, Hunan, Peoples R China C3 - Hunan Normal University C3 - Hunan Normal University FU - National 973 Project of China [2007CB516809, 200703914203]; National Natural Science Foundation of China [30770437] +FX - The authors thank all the members of our group for kindly help and suggestions This work was supported by a grant from National 973 Project of China (2007CB516809, 200703914203), and National Natural Science Foundation of China (30770437) +PU - SAGE PUBLICATIONS INC +PI - THOUSAND OAKS +PA - 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA +SN - 0963-6897 +SN - 1555-3892 +J9 - CELL TRANSPLANT +JI - Cell Transplant. +PY - 2010 +VL - 19 +IS - 2 +SP - 133 +EP - 146 +DO - 10.3727/096368910X492607 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000276961300002 +N1 - Times Cited in Web of Science Core Collection: 27 +Total Times Cited: 29 +Cited Reference Count: 62 +ER - + +TY - JOUR +AU - Jia, J +AU - Yu, Y +AU - Deng, JH +AU - Robinson, N +AU - Bovey, M +AU - Cui, YH +AU - Liu, HR +AU - Ding, W +AU - Wu, HG +AU - Wang, XM +TI - A review of Omics research in acupuncture: The relevance and future prospects for understanding the nature of meridians and acupoints +T2 - JOURNAL OF ETHNOPHARMACOLOGY +LA - English +KW - Acupuncture-moxibustion +KW - Meridian system +KW - Acupoints +KW - Omics +KW - Systems biology +KW - GENE-EXPRESSION PROFILE +KW - AGING-RELATED CHANGES +KW - PROTEOMIC ANALYSIS +KW - MICROARRAY ANALYSIS +KW - NEUROPATHIC PAIN +KW - MESSENGER-RNA +KW - ELECTROACUPUNCTURE +KW - STIMULATION +KW - MEDICINE +KW - BRAIN +AB - Relevance: Acupuncture is an intrinsic part of traditional Chinese medicine. The current understanding of the acupuncture meridian system, acupoints and the potential utilizing Omics technologies are summarized in this review. + Material and methods: A systematic search for acupuncture involving Omics technologies was carried out using multiple online literature databases. The records retrieved were from the full collections of each database dated to September 2011. Data produced from functional genomic technologies were extracted from the collected acupuncture/moxibustion studies and subjected to evaluation. Analyses and comments were summarized on the advances in experimental research in acupuncture/moxibustion-related studies, and the future for strategies and approaches in the era of functional genomics highlighted. + Results: An overview of articles indicated that several diseases or symptoms with evidence of effectiveness had been piloted for using functional genomic technologies, such as Parkinson's disease, allergic disorders, pain, and spinal cord injury, most of which are chronic "difficult diseases". High-throughput genomic and proteomic profiling of gene expression in tissues has been able to identify potential candidates for the effects of acupuncture and provide valuable information toward understanding the possible mechanisms of the therapy. However, without further holistic and sophisticated analyses in the context of metabolomics and systems biology, the current attempts and the foreseeable developments appear to be insufficient to produce firm conclusions. Noticeably, the recent rapid advances in functional molecular imaging targeting specific metabolites have shown great promise and if combined with other post-genomic technologies, could be extremely helpful for the acupuncture studies in human subjects. + Conclusion: This review suggest that disease-oriented studies using the approach of multi-indexed high-throughput technologies and systems biology analyses will be a preferred strategy for future acupuncture/moxibustion research. (C) 2012 Elsevier Ireland Ltd. All rights reserved. +AD - Capital Med Univ, Dept Biochem & Mol Biol, Beijing 100069, Peoples R China AD - Capital Med Univ, Dept Physiol, Beijing 100069, Peoples R China AD - London S Bank Univ, Fac Hlth & Social Care, London SE1 0AA, England AD - British Acupuncture Council, London W12 9HQ, England AD - Shanghai Inst Acupuncture Moxibust & Meridians, Shanghai 200030, Peoples R China C3 - Capital Medical University C3 - Capital Medical University C3 - London South Bank University FU - Work package 8 of the FP7 Good Practice in Traditional Chinese Medicine Research in the Post-genomic Era [223154]; National Natural Science Foundation of China [81072858]; "973" project [2011CB504100] +FX - We sincerely thank to Dr. Ning Li (Capital Medical University), Dr. Karen Pilkington (University of Westminster) and Dr Kah-Tong Seow for their contributions to the data collection, the literature search strategy and input on systems biology, respectively. This work was supported by Work package 8 of the FP7 Good Practice in Traditional Chinese Medicine Research in the Post-genomic Era (223154). This work was also supported by the National Natural Science Foundation of China (81072858) and the "973" project (2011CB504100). +PU - ELSEVIER IRELAND LTD +PI - CLARE +PA - ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND +SN - 0378-8741 +SN - 1872-7573 +J9 - J ETHNOPHARMACOL +JI - J. Ethnopharmacol. +DA - APR 10 +PY - 2012 +VL - 140 +IS - 3 +SP - 594 +EP - 603 +DO - 10.1016/j.jep.2012.01.034 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000302844100016 +N1 - Times Cited in Web of Science Core Collection: 34 +Total Times Cited: 36 +Cited Reference Count: 99 +ER - + +TY - JOUR +AU - Wei, Y +AU - Fang, CL +AU - Liu, SJ +AU - Yang, WQ +AU - Wei, LS +AU - Lei, XJ +AU - Hu, F +AU - Huang, HY +AU - Li, W +AU - Chen, W +AU - Li, LM +AU - Long, YS +TI - Long-term moderate exercise enhances specific proteins that constitute neurotrophin signaling pathway: A TMT-based quantitative proteomic analysis of rat plasma +T2 - JOURNAL OF PROTEOMICS +LA - English +KW - Physical exercise +KW - Neurotrophin +KW - Plasma +KW - Proteomics +KW - ACUTE ISCHEMIC-STROKE +KW - PHYSICAL-EXERCISE +KW - POTENTIAL BIOMARKERS +KW - INTEGRATIVE BIOLOGY +KW - ALZHEIMERS-DISEASE +KW - HEALTH-BENEFITS +KW - SPINAL-CORD +KW - AGED RATS +KW - BDNF +KW - EXPRESSION +AB - Physical exercise has been reported to increase neurotrophin in brain tissues as hippocampus as well as increased neurotrophic level peripherally in blood plasma and might have an effect on/or affect molecular processes of energy metabolism (and homeostasis). In this study, using quantitative proteomic analysis, we obtained a plasma protein profile from the rat with long-term moderate exercise. A total of 752 proteins were identified in the plasma. Among them, 54 proteins were significant up-regulated and 47 proteins were down-regulated in the plasma of exercise group compared with the control group. Bioinformatic analyses showed that these altered proteins are widely involved in multiple biological processes, molecular functions and cellular components, which connect with 11 signaling pathways. Interestingly, 5 up-regulated proteins Raplb, PTPN11, ARHGDIA, Cdc42 and YWHAE, confirmed by Western blots, are involved in the neurotrophin signaling pathway which shows the lowest P value among the identified pathways. Further analyses showed that the 5 neurotrophin-signaling-pathway-related proteins participate in two important protein-protein interaction networks associated to cell survival and apoptosis, axonal development, synapse formation and plasticity. This study provides an exercise-induced plasma protein profile, suggesting that long-term exercise enhances the proteins involved in neurotrophin signaling pathway which may contribute to health benefit. + Significance: Physical activity contributes to myriad benefits on body health across the lifespan. The changes in plasma proteins after chronic moderate exercise may be used as biomarkers for health and may also play important roles in increase of cardiovascular fitness, enhancement of immune competence, prevention of obesity, decrease of risk for neurological disorders, cancer, stroke, diabetes and other metabolic disorders. Using a TMT-based proteomic method, this study identified 101 altered proteins in the plasma of rats after long-term moderate treadmill running, which may provide novel biomarkers for further investigation of the underlying mechanism of physical exercise. We confirmed that exercise enhances 5 proteins of the neurotrophin signaling pathway that may contribute to health benefits. +AD - Guangzhou Sports Univ, Ctr Sci Res, 1268 Guangzhou Ave Middle, Guangzhou 510500, Guangdong, Peoples R China AD - Guangzhou Sports Univ, Inst Exercise & Hlth, 1268 Guangzhou Ave Middle, Guangzhou 510500, Guangdong, Peoples R China AD - Guangzhou Med Univ, Inst Neurosci, 250 Changgang East Rd, Guangzhou 510260, Guangdong, Peoples R China AD - Guangzhou Med Univ, Affiliated Hosp 2, 250 Changgang East Rd, Guangzhou 510260, Guangdong, Peoples R China AD - Shanghai Appl Prot Technol, Shanghai 200233, Peoples R China C3 - Guangzhou Sport University C3 - Guangzhou Sport University C3 - Guangzhou Medical University C3 - Guangzhou Medical University FU - Innovative Academic Teams of Guangzhou Education System [1201610025]; National Natural Science Foundation of China [81671112] +FX - We appreciate Shanghai Applied Protein Technology (Shanghai, China) for the technical support of LC-MS/MS experiment. This work is supported by grants from the Innovative Academic Teams of Guangzhou Education System (Grant 1201610025) and the National Natural Science Foundation of China (Grant 81671112). +PU - ELSEVIER SCIENCE BV +PI - AMSTERDAM +PA - PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS +SN - 1874-3919 +SN - 1876-7737 +J9 - J PROTEOMICS +JI - J. Proteomics +DA - AUG 15 +PY - 2018 +VL - 185 +SP - 39 +EP - 50 +DO - 10.1016/j.jprot.2018.06.017 +WE - Science Citation Index Expanded (SCI-EXPANDED) WE - Social Science Citation Index (SSCI) AN - WOS:000440770300004 +N1 - Times Cited in Web of Science Core Collection: 20 +Total Times Cited: 21 +Cited Reference Count: 67 +ER - + +TY - JOUR +AU - McGurk, L +AU - Lee, VM +AU - Trojanowksi, JQ +AU - Van Deerlin, VM +AU - Lee, EB +AU - Bonini, NM +TI - Poly-A Binding Protein-1 Localization to a Subset of TDP-43 Inclusions in Amyotrophic Lateral Sclerosis Occurs More Frequently in Patients Harboring an Expansion in C9orf72 +T2 - JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY +LA - English +KW - Amyotrophic lateral sclerosis +KW - ATXN2 +KW - C9orf72 +KW - FUS +KW - Inclusion +KW - Motor neuron +KW - PABP-1 +KW - Stress granule +KW - TDP-43 +KW - FRONTOTEMPORAL LOBAR DEGENERATION +KW - TAR-DNA-BINDING +KW - POLYGLUTAMINE EXPANSIONS +KW - BASOPHILIC INCLUSIONS +KW - HEXANUCLEOTIDE REPEAT +KW - INCREASED RISK +KW - SARCOMA FUS +KW - MUTATIONS +KW - ALS +KW - DISEASE +AB - Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease in which the loss of spinal cord motor neurons leads to paralysis and death within a few years of clinical disease onset. In almost all cases of ALS, transactive response DNA binding protein of 43 kDa (TDP-43) forms cytoplasmic neuronal inclusions. A second causative gene for a subset of ALS is fused in sarcoma, an RNA binding protein that also forms cytoplasmic inclusions in spinal cord motor neurons. Poly-A binding protein-1 (PABP-1) is a marker of stress granules (i.e. accumulations of proteins and RNA indicative of translational arrest in cells under stress). We report on the colocalization of PABP-1 to both TDP-43 and fused-in-sarcoma inclusions in 4 patient cohorts: ALS without a mutation, ALS with an intermediate polyglutamine repeat expansion in ATXN2, ALS with a GGGGCC hexanucleotide repeat expansion in C9orf72, and ALS with basophilic inclusion body disease. Notably, PABP-1 colocalization to TDP-43 was twice as frequent in ALS with C9orf72 expansions compared to ALS with no mutation. This study highlights PABP-1 as a protein that is important to the pathology of ALS and indicates that the proteomic profile of TDP-43 inclusions in ALS may differ depending on the causative genetic mutation. +AD - Univ Penn, Dept Biol, Philadelphia, PA 19104 USA AD - Stellar Chance Labs, Translat Neuropathol Res Lab, Philadelphia, PA USA AD - Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA USA C3 - University of Pennsylvania C3 - University of Pennsylvania FU - National Institutes of Health [R01NS073660, AG10124, AG32953, AG039510] +FX - This study was supported by National Institutes of Health Grant Nos. R01NS073660 (Nancy M. Bonini), AG10124 and AG32953 (John Q. Trojanowksi, Vivianna M. Van Deerlin, Virginia M. Lee, and Edward B. Lee), and AG039510 (Edward B. Lee). +PU - OXFORD UNIV PRESS INC +PI - CARY +PA - JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA +SN - 0022-3069 +SN - 1554-6578 +J9 - J NEUROPATH EXP NEUR +JI - J. Neuropathol. Exp. Neurol. +DA - SEP +PY - 2014 +VL - 73 +IS - 9 +SP - 837 +EP - 845 +DO - 10.1097/NEN.0000000000000102 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000341398300003 +N1 - Times Cited in Web of Science Core Collection: 46 +Total Times Cited: 52 +Cited Reference Count: 47 +ER - + +TY - JOUR +AU - Xu, XJ +AU - Qiu, Y +AU - Liu, ZY +AU - Zhang, R +AU - Yu, H +AU - Wang, ML +AU - Chen, S +AU - Xu, GW +AU - Shao, YP +AU - Le, WD +TI - Integrative analysis of metabolomics and proteomics unravels purine metabolism dysregulation in the SOD1G93A mouse model of amyotrophic lateral sclerosis +T2 - NEUROBIOLOGY OF DISEASE +LA - English +KW - Amyotrophic lateral sclerosis +KW - MetabolomicsProteomics +KW - Liquid chromatography-mass spectrometry +KW - Purine metabolism +KW - Folate and methionine cycle +KW - MOTOR-NEURON DEGENERATION +KW - ONE-CARBON METABOLISM +KW - HIPPOCAMPAL SLICES +KW - CELL-DEATH +KW - PATHWAY ACTIVATION +KW - 26S PROTEASOMES +KW - LINOLENIC ACID +KW - GUANOSINE +KW - CAFFEINE +KW - FOLATE +AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive paralysis of limbs and bulb in patients, the cause of which remains unclear. Accumulating studies suggest that motor neuron degeneration is associated with systemic metabolic impairment in ALS. However, the metabolic reprogramming and underlying mechanism in the longitudinal progression of the disease remain poorly understood. In this study, we aimed to investigate the molecular changes at both metabolic and proteomic levels during disease progression to identify the most critical metabolic pathways and underlying mechanisms involved in ALS pathophysiological changes. Utilizing liquid chromatography-mass spectrometry-based metabolomics, we analyzed the metabolites' levels of plasma, lumbar spinal cord, and motor cortex from SOD1(G93A) mice and wildtype (WT) littermates at different stages. To elucidate the regulatory network underlying metabolic changes, we further analyzed the proteomics profile in the spinal cords of SOD1(G93A) and WT mice. A group of metabolites implicated in purine metabolism, methionine cycle, and glycolysis were found differentially expressed in ALS mice, and abnormal expressions of enzymes involved in these metabolic pathways were also confirmed. Notably, we first demonstrated that dysregulation of purine metabolism might contribute to the pathogenesis and disease progression of ALS. Furthermore, we discovered that fatty acid metabolism, TCA cycle, arginine and proline metabolism, and folate-mediated one-carbon metabolism were also significantly altered in this disease. The identified differential metabolites and proteins in our study could complement existing data on metabolic reprogramming in ALS, which might provide new insight into the pathological mechanisms and novel therapeutic targets of ALS. +AD - Univ Elect Sci & Technol China, Sichuan Acad Med Sci, Inst Neurol, Sch Med,Sichuan Prov Peoples Hosp, Chengdu 611731, Peoples R China AD - Dalian Med Univ, Affiliated Hosp 1, Liaoning Prov Key Lab Res Pathogen Mech Neurol Di, Dalian 116021, Peoples R China AD - Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, 457 Zhongshan Rd, Dalian 116023, Peoples R China AD - Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Neurol, Sch Med, Shanghai 200020, Peoples R China C3 - University of Electronic Science & Technology of China C3 - Sichuan Provincial People's Hospital C3 - Dalian Medical University C3 - Chinese Academy of Sciences C3 - Dalian Institute of Chemical Physics, CAS C3 - Shanghai Jiao Tong University FU - National Natural Sciences Foundation of China [NSFC 22004013, 82271524]; Key R & D Program of Guangdong Provincial [2018B030337001]; Doctoral Scientific Research Foundation of Liaoning Science and Technology Department [2020-BS-200]; Central Guidance on Local Science and Technology Development Fund of Dalian Science and Technology Bureau +FX - This work was supported by funding from the National Natural Sciences Foundation of China [grant numbers NSFC 22004013, 82271524]; Key R & D Program of Guangdong Provincial [grant numbers 2018B030337001]; Doctoral Scientific Research Foundation of Liaoning Science and Technology Department [grant numbers 2020-BS-200] and the Central Guidance on Local Science and Technology Development Fund of Dalian Science and Technology Bureau. +PU - ACADEMIC PRESS INC ELSEVIER SCIENCE +PI - SAN DIEGO +PA - 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA +SN - 0969-9961 +SN - 1095-953X +J9 - NEUROBIOL DIS +JI - Neurobiol. Dis. +DA - JUN 1 +PY - 2023 +VL - 181 +C7 - 106110 +DO - 10.1016/j.nbd.2023.106110 +C6 - APR 2023 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000975738500001 +N1 - Times Cited in Web of Science Core Collection: 2 +Total Times Cited: 2 +Cited Reference Count: 87 +ER - + +TY - JOUR +AU - Leao, LKR +AU - Bittencourt, LO +AU - Oliveira, ACA +AU - Nascimento, PC +AU - Ferreira, MKM +AU - Miranda, GHN +AU - Ferreira, RD +AU - Eiró-Quirino, L +AU - Puty, B +AU - Dionizio, A +AU - Cartágenes, SC +AU - Freire, MAM +AU - Buzalaf, MAR +AU - Crespo-Lopez, ME +AU - Maia, CSF +AU - Lima, RR +TI - Lead-Induced Motor Dysfunction Is Associated with Oxidative Stress, Proteome Modulation, and Neurodegeneration in Motor Cortex of Rats +T2 - OXIDATIVE MEDICINE AND CELLULAR LONGEVITY +LA - English +KW - LIPID-PEROXIDATION PRODUCTS +KW - ENERGY-METABOLISM +KW - BARREL FIELD +KW - EXPOSURE +KW - IMPAIRMENT +KW - CELLUGYRIN +KW - SYNAPSINS +KW - ISCHEMIA +KW - DAMAGE +AB - Lead (Pb) is a toxic metal with great neurotoxic potential. The aim of this study was to investigate the effects of a long-term Pb intoxication on the global proteomic profile, oxidative biochemistry and neuronal density in motor cortex of adult rats, and the possible outcomes related to motor functions. For this, Wistar rats received for 55 days a dose of 50 mg/Kg of Pb acetate by intragastric gavage. Then, the motor abilities were evaluated by open field and inclined plane tests. To investigate the possible oxidative biochemistry modulation, the levels of pro-oxidant parameters as lipid peroxidation and nitrites were evaluated. The global proteomic profile was evaluated by ultraefficiency liquid chromatography system coupled with mass spectrometry (UPLC/MS) followed by bioinformatic analysis. Moreover, it was evaluated the mature neuron density by anti-NeuN immunostaining. The statistical analysis was performed through Student's t-test, considering p<0.05. We observed oxidative stress triggering by the increase in malonaldehyde and nitrite levels in motor cortex. In the proteomic analysis, the motor cortex presented alterations in proteins associated with neural functioning, morphological organization, and neurodegenerative features. In addition, it was observed a decrease in the number of mature neurons. These findings, associated with previous evidences observed in spinal cord, cerebellum, and hippocampus under the same Pb administration protocol, corroborate with the motor deficits in the rats towards Pb. Thus, we conclude that the long-term administration to Pb in young Wistar rats triggers impairments at several organizational levels, such as biochemical and morphological, which resulted in poor motor performance. +AD - Fed Univ Para, Lab Funct & Struct Biol, Inst Biol Sci, Belem, Para, Brazil AD - Univ Sao Paulo, Bauru Dent Sch, Dept Biol Sci, Bauru, SP, Brazil AD - Fed Univ Para, Pharm Fac, Inst Hlth Sci, Lab Pharmacol Inflammat & Behav, Belem, Para, Brazil AD - Univ State Rio Grande do Norte, Grad Program Hlth & Soc, Mossoro, RN, Brazil AD - Fed Univ Para, Inst Biol Sci, Lab Mol Pharmacol, Belem, Para, Brazil C3 - Universidade Federal do Para C3 - Universidade de Sao Paulo C3 - Universidade Federal do Para C3 - Universidade do Estado do Rio Grande do Norte (UERN) C3 - Universidade Federal do Para FU - Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [001]; CNPq +FX - We thank to Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) for partial financing (Code 001), the Pro-reitoria de Pesquisa e Pos-graduacao from Federal University of Para for the APC payment, and to the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) from Brazilian Ministry of Science, Technology, Innovation and Communications (MCTI). MECL and CSFM thank to CNPq for their Research Productivity Grant. +PU - HINDAWI LTD +PI - LONDON +PA - ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND +SN - 1942-0900 +SN - 1942-0994 +J9 - OXID MED CELL LONGEV +JI - Oxidative Med. Cell. Longev. +DA - OCT 7 +PY - 2021 +VL - 2021 +C7 - 5595047 +DO - 10.1155/2021/5595047 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000723155300006 +N1 - Times Cited in Web of Science Core Collection: 14 +Total Times Cited: 15 +Cited Reference Count: 63 +ER - + +TY - JOUR +AU - Lindholm, D +AU - Eriksson, O +AU - Korhonen, L +TI - Mitochondrial proteins in neuronal degeneration +T2 - BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS +LA - English +KW - mitochondria +KW - neurological disease +KW - paraplegin +KW - omi +KW - AIF +KW - Ucp-2 +KW - APOPTOSIS-INDUCING FACTOR +KW - TRANSIENT CEREBRAL-ISCHEMIA +KW - MND2 MUTANT MICE +KW - CASPASE ACTIVATION +KW - SERINE-PROTEASE +KW - CELL-DEATH +KW - PERMEABILITY TRANSITION +KW - HYPOXIA-ISCHEMIA +KW - OXIDATIVE STRESS +KW - CYTOCHROME-C +AB - In this review. we highlight recent findings about the role of some mitochondrial proteins in neurological diseases. Studies in mice gene-deleted for Omi/HtrA2 and AIF showed the involvement of these mitochondrial proteins in, selective cell degeneration in the spinal cord and brain. In humans, mutations in the mitochondrial protein, Paraplegin, cause an autosomal form of hereditary spastic paraplegia with an enhanced sensitivity to oxidative stress. Reactive oxygen species and decreased respiratory chain activity in mitochondria also contribute to common neurological diseases. The mitochondrial uncoupling protein, Ucp-2, was found to be neuroprotective in experimental stroke and brain trauma. Recent proteomic and profiling studies have revealed the existence of additional mitochondrial proteins with unknown functions. The elucidation of the physiological functions of mitochondrial proteins may lead to new insights into the role of these organelles in cell degeneration and to identification of novel drug targets for the prevention and treatment of different diseases. (C) 2004 Elsevier Inc. All rights reserved. +AD - Uppsala Univ, Ctr Biomed, Dept Neurosci, S-75123 Uppsala, Sweden AD - Minerva Res Inst, Helsinki 00290, Finland AD - Univ Helsinki, Inst Biomed Biochem, Helsinki, Finland C3 - Uppsala University C3 - University of Helsinki PU - ACADEMIC PRESS INC ELSEVIER SCIENCE +PI - SAN DIEGO +PA - 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA +SN - 0006-291X +SN - 1090-2104 +J9 - BIOCHEM BIOPH RES CO +JI - Biochem. Biophys. Res. Commun. +DA - SEP 3 +PY - 2004 +VL - 321 +IS - 4 +SP - 753 +EP - 758 +DO - 10.1016/j.bbrc.2004.06.138 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000223381100001 +N1 - Times Cited in Web of Science Core Collection: 37 +Total Times Cited: 47 +Cited Reference Count: 45 +ER - + +TY - JOUR +AU - Mallah, K +AU - Zibara, K +AU - Kerbaj, C +AU - Eid, A +AU - Khoshman, N +AU - Ousseily, Z +AU - Kobeissy, A +AU - Cardon, T +AU - Cizkova, D +AU - Kobeissy, F +AU - Fournier, I +AU - Salzet, M +TI - Neurotrauma investigation through spatial omics guided by mass spectrometry imaging: Target identification and clinical applications +T2 - MASS SPECTROMETRY REVIEWS +LA - English +KW - mass spectrometry imaging +KW - spatial omics approaches +KW - spinal cord injury +KW - trauma brain injury +KW - TRAUMATIC BRAIN-INJURY +KW - LASER-CAPTURE MICRODISSECTION +KW - PARAFILM-ASSISTED MICRODISSECTION +KW - SPINAL-CORD-INJURY +KW - RAT-BRAIN +KW - OXIDATIVE LIPIDOMICS +KW - SYSTEMS BIOLOGY +KW - MOUSE MODEL +KW - MALDI MS +KW - NEUROPROTEOMICS +AB - Traumatic brain injury (TBI) represents one of the major public health concerns worldwide due to the increase in TBI incidence as a result of injuries from daily life accidents such as sports and motor vehicle transportation as well as military-related practices. This type of central nervous system trauma is known to predispose patients to several neurological disorders such as Parkinson's disease, Alzheimer's disease, chronic trauamatic encephalopathy, and age-related Dementia. Recently, several proteomic and lipidomic platforms have been applied on different TBI studies to investigate TBI-related mechanisms that have broadened our understanding of its distinct neuropathological complications. In this study, we provide an updated comprehensive overview of the current knowledge and novel perspectives of the spatially resolved microproteomics and microlipidomics approaches guided by mass spectrometry imaging used in TBI studies and its applications in the neurotrauma field. In this regard, we will discuss the use of the spatially resolved microproteomics and assess the different microproteomic sampling methods such as laser capture microdissection, parafilm assisted microdissection, and liquid microjunction extraction as accurate and precise techniques in the field of neuroproteomics. Additionally, we will highlight lipid profiling applications and their prospective potentials in characterizing molecular processes involved in the field of TBI. Specifically, we will discuss the phospholipid metabolism acting as a precursor for proinflammatory molecules such as eicosanoids. Finally, we will survey the current state of spatial neuroproteomics and microproteomics applications and present the various studies highlighting their findings in these fields. +AD - Med Univ South Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA AD - Lebanese Univ, PRASE, Beirut, Lebanon AD - UnivLille, INSERM, CHU Lille, U1192,Lab Proteom Reponse Inflammatoire & Spectro, F-59000 Lille, France AD - Lebanese Univ, Dept Biol, Fac Sci 1, Beirut, Lebanon AD - Qatar Univ, Dept Basic Med Sci, QU Hlth, Doha, Qatar AD - Amer Univ Beirut, Dept Biochem & Mol Genet, Fac Med, Beirut, Lebanon AD - Univ Vet Med & Pharm Kosice, Ctr Expt & Clin Regenerat Med, Kosice, Slovakia AD - Inst Univ France, Paris, France C3 - Medical University of South Carolina C3 - Lebanese University C3 - Universite de Lille C3 - CHU Lille C3 - Institut National de la Sante et de la Recherche Medicale (Inserm) C3 - Lebanese University C3 - Qatar University C3 - American University of Beirut C3 - University of Veterinary Medicine Kosice C3 - Institut Universitaire de France FU - Association of Scientific Orientation and Specialization (ASOS) [APVV 19-0193, VEGA 1/0376/20]; Ministere de L'Education Nationale, de L'Enseignement Superieur et de la Recherche, Universite de Lille, Region Hauts de France, INSERM +FX - This study was supported by grants from the Ministere de L'Education Nationale, de L'Enseignement Superieur et de la Recherche, Universite de Lille, Region Hauts de France, INSERM. K.M. received a scholarship from the Association of Scientific Orientation and Specialization (ASOS), APVV 19-0193, VEGA 1/0376/20. +PU - WILEY +PI - HOBOKEN +PA - 111 RIVER ST, HOBOKEN 07030-5774, NJ USA +SN - 0277-7037 +SN - 1098-2787 +J9 - MASS SPECTROM REV +JI - Mass Spectrom. Rev. +DA - JAN +PY - 2023 +VL - 42 +IS - 1 +SP - 189 +EP - 205 +DO - 10.1002/mas.21719 +C6 - JUL 2021 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000678662200001 +N1 - Times Cited in Web of Science Core Collection: 8 +Total Times Cited: 9 +Cited Reference Count: 116 +ER - + +TY - JOUR +AU - Mollá, B +AU - Muñoz-Lasso, DC +AU - Calap, P +AU - Fernandez-Vilata, A +AU - de la Iglesia-Vaya, M +AU - Pallardó, FV +AU - Moltó, MD +AU - Palau, F +AU - Gonzalez-Cabo, P +TI - Phosphodiesterase Inhibitors Revert Axonal Dystrophy in Friedreich's Ataxia Mouse Model +T2 - NEUROTHERAPEUTICS +LA - English +KW - FRDA +KW - axonal degeneration +KW - G protein-coupled receptor (GPCR) +KW - Ca2+ signaling +KW - PDE inhibitors +KW - DORSAL-ROOT GANGLIA +KW - OXIDATIVE STRESS +KW - MITOCHONDRIAL BIOGENESIS +KW - FUNCTIONAL RECOVERY +KW - SMOOTH-MUSCLE +KW - FRATAXIN +KW - DEFICIENCY +KW - EXPRESSION +KW - NEUROPATHY +KW - RECEPTOR +AB - Friedreich's ataxia (FRDA) is a neurodegenerative disorder caused by an unstable GAA repeat expansion within intron 1 of the FXN gene and characterized by peripheral neuropathy. A major feature of FRDA is frataxin deficiency with the loss of large sensory neurons of the dorsal root ganglia (DRG), namely proprioceptive neurons, undergoing dying-back neurodegeneration with progression to posterior columns of the spinal cord and cerebellar ataxia. We used isolated DRGs from a YG8R FRDA mouse model and C57BL/6J control mice for a proteomic study and a primary culture of sensory neurons from DRG to test novel pharmacological strategies. We found a decreased expression of electron transport chain (ETC) proteins, the oxidative phosphorylation (OXPHOS) system and antioxidant enzymes, confirming a clear impairment in mitochondrial function and an oxidative stress-prone phenotype. The proteomic profile also showed a decreased expression in Ca2+ signaling related proteins and G protein-coupled receptors (GPCRs). These receptors modulate intracellular cAMP/cGMP and Ca2+ levels. Treatment of frataxin-deficient sensory neurons with phosphodiesterase (PDE) inhibitors was able to restore improper cytosolic Ca2+ levels and revert the axonal dystrophy found in DRG neurons of YG8R mice. In conclusion, the present study shows the effectiveness of PDE inhibitors against axonal degeneration of sensory neurons in YG8R mice. Our findings indicate that PDE inhibitors may become a future FRDA pharmacological treatment. +AD - CIBERER, Valencia 46010, Spain AD - CSIC, IBV, Valencia 46010, Spain AD - Univ Valencia, Fac Med & Dent, Dept Physiol, Avda Blasco Ibanez, Valencia 46010, Spain AD - Associated Unit Rare Dis INCLIVA CIPF, Valencia 46010, Spain AD - Univ Valencia, Dept Genet, Campus Burjassot, E-46100 Valencia, Spain AD - Joint Unit FISABIO, Brain Connect Lab, Valencia 46012, Spain AD - Prince Felipe Res Ctr CIPF, Valencia 46012, Spain AD - Hosp Sagunto CEIB CSUSP, Reg Minist Hlth Valencia, Valencia 46500, Spain AD - CIBER Salud Mental CIBERSAM, Valencia 46010, Spain AD - Biomed Res Inst INCLIVA, Valencia 46010, Spain AD - Inst Recerca St Joan de Deu, Barcelona 08950, Spain AD - Hosp St Joan de Deu, Dept Genet & Mol Med, Barcelona 08950, Spain AD - Hosp St Joan de Deu, IPER, Barcelona 08950, Spain AD - Univ Barcelona, Sch Med, Dept Pediat, E-08036 Barcelona, Spain C3 - CIBER - Centro de Investigacion Biomedica en Red C3 - CIBERER C3 - Consejo Superior de Investigaciones Cientificas (CSIC) C3 - CSIC - Instituto de Biomedicina de Valencia (IBV) C3 - University of Valencia C3 - University of Valencia C3 - Prince Felipe Research Center C3 - CIBER - Centro de Investigacion Biomedica en Red C3 - CIBERSAM C3 - University of Barcelona C3 - University of Barcelona C3 - University of Barcelona FU - Spanish Ministry of Economy and Competitiveness [PI11/00678, SAF2015-66625-R]; Instituto de Salud Carlos III (ISCIII)-Subdireccion General de Evaluacion y Fomento de la Investigacion; FEDER funds; Fundacion Ramon Areces [CIVP18A3899]; Generalitat Valenciana [PROMETEOII/2014/067, PROMETEOII/2014/029, ACIF/2014/090, ACOMP/2014/058] +FX - This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (Grant No. PI11/00678; SAF2015-66625-R) within the framework of the National R + D + I Plan and cofunded by the Instituto de Salud Carlos III (ISCIII)-Subdireccion General de Evaluacion y Fomento de la Investigacion and FEDER funds, Fundacion Ramon Areces (CIVP18A3899), and the Generalitat Valenciana (PROMETEOII/2014/067, PROMETEOII/2014/029, ACIF/2014/090, ACOMP/2014/058). CIBERER is an initiative developed by the Instituto de Salud Carlos III in cooperative and translational research on rare diseases. We would like to thank the staff of the CIBERER Biobank (Valencia, Spain) for their help in generating the lymphoblastoid cell lines (LCLs). +PU - SPRINGER +PI - NEW YORK +PA - 233 SPRING ST, NEW YORK, NY 10013 USA +SN - 1933-7213 +SN - 1878-7479 +J9 - NEUROTHERAPEUTICS +JI - Neurotherapeutics +DA - APR +PY - 2019 +VL - 16 +IS - 2 +SP - 432 +EP - 449 +DO - 10.1007/s13311-018-00706-z +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000471053500015 +N1 - Times Cited in Web of Science Core Collection: 9 +Total Times Cited: 10 +Cited Reference Count: 74 +ER - + +TY - JOUR +AU - An, D +AU - Wei, XW +AU - Li, H +AU - Gu, H +AU - Huang, TC +AU - Zhao, GF +AU - Liu, B +AU - Wang, WL +AU - Chen, LZ +AU - Ma, W +AU - Zhang, HN +AU - Cao, SY +AU - Yuan, ZW +TI - Identification of PCSK9 as a novel serum biomarker for the prenatal diagnosis of neural tube defects using iTRAQ quantitative proteomics +T2 - SCIENTIFIC REPORTS +LA - English +KW - AMNIOTIC-FLUID +KW - CEREBROSPINAL-FLUID +KW - DOWN-SYNDROME +KW - EXPRESSION +KW - FETUSES +KW - PROFILE +KW - PLASMA +AB - To identify candidate serum molecule biomarkers for the non-invasive early prenatal diagnosis of neural tube defects (NTDs), we employed an iTRAQ-based quantitative proteomic approach to analyze the proteomic changes in serum samples from embryonic day (E) 11 and E13 pregnant rats with spina bifida aperta (SBA) induced by all-trans retinoic acid. Among the 390 proteins identified, 40 proteins at E11 and 26 proteins at E13 displayed significant differential expression in the SBA groups. We confirmed 5 candidate proteins by ELISA. We observed the space-time expression changes of proprotein convertase subtilisin/kexin type 9 (PCSK9) at different stages of fetal development, including a marked decrease in the sera of NTD pregnancies and gradual increase in the sera of normal pregnancies with embryonic development. PCSK9 demonstrated the diagnostic efficacy of potential NTD biomarkers [with an area under the receiver operating characteristic curve of 0.763, 95% CI: 065-0.88]. Additionally, PCSK9 expression in the spinal cords and placentas of SBA rat fetuses was markedly decreased. PCSK9 could serve as a novel molecular biomarker for the non-invasive prenatal screening of NTDs and may be involved in the pathogenesis of NTDs at critical periods of fetal development. +AD - China Med Univ, Shengjing Hosp, Key Lab Hlth Minist Congenital Malformat, Shenyang 110004, Peoples R China AD - China Med Univ, Affiliated Hosp 1, Dept Pediat, Shenyang 110001, Peoples R China AD - China Med Univ, Shengjing Hosp, Dept Pediat Surg, Shenyang 110004, Peoples R China C3 - China Medical University C3 - China Medical University C3 - China Medical University FU - National Natural Foundation of China [81370717, 81171072]; National Basic Research Program of China (973 program) [2013CB945402]; Program for Liaoning Innovative Research Team in University [LT2013016] +FX - This study was supported by the National Natural Foundation of China. (Grant number: 81370717, 81171072), the National Basic Research Program of China (973 program, No. 2013CB945402), and the Program for Liaoning Innovative Research Team in University (LT2013016). +PU - NATURE PORTFOLIO +PI - BERLIN +PA - HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY +SN - 2045-2322 +J9 - SCI REP-UK +JI - Sci Rep +DA - DEC 22 +PY - 2015 +VL - 5 +C7 - 17559 +DO - 10.1038/srep17559 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000367033600001 +N1 - Times Cited in Web of Science Core Collection: 42 +Total Times Cited: 45 +Cited Reference Count: 41 +ER - + +TY - JOUR +AU - Lin, BC +AU - Phung, TH +AU - Higgins, NR +AU - Greenslade, JE +AU - Prado, MA +AU - Finley, D +AU - Karbowski, M +AU - Polster, BM +AU - Monteiro, MJ +TI - ALS/FTD mutations in UBQLN2 are linked to mitochondrial dysfunction through loss-of-function in mitochondrial protein import +T2 - HUMAN MOLECULAR GENETICS +LA - English +KW - OXIDATIVE STRESS +KW - AUTOPHAGY +KW - FUSION +KW - PHOSPHORYLATION +KW - UBIQUILINS +KW - CHAPERONE +KW - CELLS +KW - IDENTIFICATION +KW - TRANSLATION +KW - DEGRADATION +AB - UBQLN2 mutations cause amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD), but the pathogenic mechanisms by which they cause disease remain unclear. Proteomic profiling identified 'mitochondrial proteins' as comprising the largest category of protein changes in the spinal cord (SC) of the P497S UBQLN2 mouse model of ALS/FTD. Immunoblots confirmed P497S animals have global changes in proteins predictive of a severe decline in mitochondrial health, including oxidative phosphorylation (OXPHOS), mitochondrial protein import and network dynamics. Functional studies confirmed mitochondria purified from the SC of P497S animals have age-dependent decline in nearly all steps of OXPHOS. Mitochondria cristae deformities were evident in spinal motor neurons of aged P497S animals. Knockout (KO) of UBQLN2 in HeLa cells resulted in changes in mitochondrial proteins and OXPHOS activity similar to those seen in the SC. KO of UBQLN2 also compromised targeting and processing of the mitochondrial import factor, TIMM44, resulting in accumulation in abnormal foci. The functional OXPHOS deficits and TIMM44-targeting defects were rescued by reexpression of WT UBQLN2 but not by ALS/FTD mutant UBQLN2 proteins. In vitro binding assays revealed ALS/FTD mutant UBQLN2 proteins bind weaker with TIMM44 than WT UBQLN2 protein, suggesting that the loss of UBQLN2 binding may underlie the import and/or delivery defect of TIMM44 to mitochondria. Our studies indicate a potential key pathogenic disturbance in mitochondrial health caused by UBQLN2 mutations. +AD - Univ Maryland, Program Neurosci, Sch Med, Baltimore, MD 21201 USA AD - Univ Maryland, Ctr Biomed Engn & Technol, Sch Med, Baltimore, MD 21201 USA AD - Univ Maryland, Dept Anat & Neurobiol, Sch Med, Baltimore, MD 21201 USA AD - Univ Maryland, Program Mol Med, Sch Med, Baltimore, MD 21201 USA AD - Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA AD - Univ Maryland, Dept Biochem & Mol Biol, Sch Med, Baltimore, MD 21201 USA AD - Univ Maryland, Ctr Shock Trauma & Anesthesiol Res, Dept Anesthesiol, Sch Med, Baltimore, MD 21201 USA C3 - University System of Maryland C3 - University of Maryland Baltimore C3 - University System of Maryland C3 - University of Maryland Baltimore C3 - University System of Maryland C3 - University of Maryland Baltimore C3 - University System of Maryland C3 - University of Maryland Baltimore C3 - Harvard University C3 - Harvard Medical School C3 - University System of Maryland C3 - University of Maryland Baltimore C3 - University System of Maryland C3 - University of Maryland Baltimore FU - NIH NINDS [R01NS098243, R01NS100008]; NIGMS grant [R01GM129584]; The Robert Packard Center for ALS Research at Johns Hopkins; National Institute of Neurological Disorders and Stroke; National Institute on Aging [R01NS098243] Funding Source: NIH RePORTER; National Institute on Aging [R01NS100008] Funding Source: NIH RePORTER +FX - The Robert Packard Center for ALS Research at Johns Hopkins and NIH NINDS grants (R01NS098243, R01NS100008 to M.J.M.); NIGMS grant (R01GM129584 to M.K.). +PU - OXFORD UNIV PRESS +PI - OXFORD +PA - GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND +SN - 0964-6906 +SN - 1460-2083 +J9 - HUM MOL GENET +JI - Hum. Mol. Genet. +DA - JUL 1 +PY - 2021 +VL - 30 +IS - 13 +SP - 1230 +EP - 1246 +DO - 10.1093/hmg/dab116 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000670929100005 +N1 - Times Cited in Web of Science Core Collection: 15 +Total Times Cited: 17 +Cited Reference Count: 83 +ER - + +TY - JOUR +AU - McCrary, MW +AU - Vaughn, NE +AU - Hlavac, N +AU - Song, YH +AU - Wachs, RA +AU - Schmidt, CE +TI - Novel Sodium Deoxycholate-Based Chemical Decellularization Method for Peripheral Nerve +T2 - TISSUE ENGINEERING PART C-METHODS +LA - English +KW - peripheral nerve +KW - decellularization +KW - acellular matrices +KW - sodium deoxycholate +KW - EXTRACELLULAR-MATRIX +KW - BIOLOGIC SCAFFOLDS +KW - SPINAL-CORD +KW - STATISTICAL-MODEL +KW - PROTEINS +KW - OUTCOMES +KW - LUNG +KW - RECONSTRUCTION +KW - ALLOGRAFTS +KW - GRAFT +AB - Decellularized peripheral nerve has been proven to be an effective clinical intervention for peripheral nerve repair and a preclinical cell carrier after spinal cord injury. However, there are currently a lack of decellularization methods for peripheral nerve that remove cells and maintain matrix similar to the previously established, clinically translated technique (the Hudson method) that relies on the discontinued Triton X-200 detergent. Therefore, the aim of this study was to optimize a novel chemical decellularization method for peripheral nerves based on the currently available anionic detergent sodium deoxycholate. Sprague Dawley rat sciatic nerves were isolated, frozen in buffered solution, and then subject to sequential washes in water, salt buffer, zwitterionic detergents sulfobetaines -10 and -16, and varying concentrations of sodium deoxycholate (SDC). To optimize DNA removal after SDC decellularization, nerves were subjected to deoxyribonuclease (DNase) incubation and salt buffer washes. Immunohistochemical results demonstrated that utilization of 3% SDC in the decellularization process preserved extracellular matrix (ECM) components and structure while facilitating significantly better removal of Schwann cells, axons, and myelin compared with the Hudson method. The addition of a 3-h DNase incubation to the 3% SDC decellularization process significantly removed cellular debris compared with the Hudson method. Proteomic analysis demonstrated that our novel decellularization method based on 3% SDC +3-h DNase used in conjunction with zwitterionic detergents, and salt buffers (new decellularization method using 3% SDC + 3-h DNase, zwitterionic detergents, and salt buffers [SDD method]) produced a similar proteomic profile compared with the Hudson method and had significantly fewer counts of cellular proteins. Finally, cytotoxicity analysis demonstrated that the SDD decellularized scaffolds do not contain significant cytotoxic residuals as eluted media supported metabolically active Schwann cells in vitro. Overall, this study demonstrates that SDD decellularization represents a novel alternative utilizing currently commercially available chemical reagents. Impact Statement Decellularized nerves are clinically relevant materials that can be used for a variety of regenerative applications such as peripheral nerve and spinal cord injury repair. However, discontinuation of key detergents used in a proven chemical decellularization process necessitates the optimization of an equivalent or better method. This research presents the field with a novel chemical decellularization method to replace the previous validated standard. Scaffolds generated from this method provide an extracellular matrix-rich material that can be used in a variety of in vitro applications to understand cellular behavior and in vivo applications to facilitate regeneration after neural injury. +AD - Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, 1275 Ctr Dr BMSB JG-42 POB 116131, Gainesville, FL 32611 USA AD - Univ Arkansas, Dept Biomed Engn, Fayetteville, AR 72701 USA AD - Univ Nebraska, Dept Biol Syst Engn, Lincoln, NE USA C3 - State University System of Florida C3 - University of Florida C3 - University of Arkansas System C3 - University of Arkansas Fayetteville C3 - University of Nebraska System C3 - University of Nebraska Lincoln PU - MARY ANN LIEBERT, INC +PI - NEW ROCHELLE +PA - 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA +SN - 1937-3384 +SN - 1937-3392 +J9 - TISSUE ENG PART C-ME +JI - Tissue Eng. Part C-Methods +DA - JAN 1 +PY - 2020 +VL - 26 +IS - 1 +SP - 23 +EP - 36 +DO - 10.1089/ten.tec.2019.0135 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000507442300003 +N1 - Times Cited in Web of Science Core Collection: 41 +Total Times Cited: 41 +Cited Reference Count: 57 +ER - + +TY - JOUR +AU - Ibrahim, MM +AU - Patwardhan, A +AU - Gilbraith, KB +AU - Moutal, A +AU - Yang, XF +AU - Chew, LA +AU - Largent-Milnes, T +AU - Malan, TP +AU - Vanderah, TW +AU - Porreca, F +AU - Khanna, R +TI - Long-lasting antinociceptive effects of green light in acute and chronic pain in rats +T2 - PAIN +LA - English +KW - Green-light phototherapy +KW - Constellation pharmacology +KW - Calcium imaging +KW - Proteomics +KW - Neuropathic pain +KW - Thermal antinociception +KW - Mechanical allodynia +KW - THERAPY INDUCES ANALGESIA +KW - STRESS-INDUCED ANALGESIA +KW - INDUCED HYPERALGESIA +KW - NEUROPATHIC PAIN +KW - PERIAQUEDUCTAL GRAY +KW - GANGLION-CELLS +KW - MODEL +KW - STIMULATION +KW - PROJECTIONS +KW - EXPRESSION +AB - Treatments for chronic pain are inadequate, and new options are needed. Nonpharmaceutical approaches are especially attractive with many potential advantages including safety. Light therapy has been suggested to be beneficial in certain medical conditions such as depression, but this approach remains to be explored for modulation of pain. We investigated the effects of light-emitting diodes (LEDs), in the visible spectrum, on acute sensory thresholds in naive rats as well as in experimental neuropathic pain. Rats receiving green LED light (wavelength 525 nm, 8 h/d) showed significantly increased paw withdrawal latency to a noxious thermal stimulus; this antinociceptive effect persisted for 4 days after termination of last exposure without development of tolerance. No apparent side effects were noted and motor performance was not impaired. Despite LED exposure, opaque contact lenses prevented antinociception. Rats fitted with green contact lenses exposed to room light exhibited antinociception arguing for a role of the visual system. Antinociception was not due to stress/anxiety but likely due to increased enkephalins expression in the spinal cord. Naloxone reversed the antinociception, suggesting involvement of central opioid circuits. Rostral ventromedial medulla inactivation prevented expression of light-induced antinociception suggesting engagement of descending inhibition. Green LED exposure also reversed thermal and mechanical hyperalgesia in rats with spinal nerve ligation. Pharmacological and proteomic profiling of dorsal root ganglion neurons from green LED-exposed rats identified changes in calcium channel activity, including a decrease in the N-type (CaV2.2) channel, a primary analgesic target. Thus, green LED therapy may represent a novel, nonpharmacological approach for managing pain. +AD - Univ Arizona, Coll Med, Dept Anesthesiol, 1501 North Campbell Dr,POB 245050, Tucson, AZ 85724 USA AD - Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA C3 - University of Arizona C3 - University of Arizona FU - Career Development Award from the University of Arizona Health Sciences; Children's Tumor Foundation NF1 Synodos grant; start- up seed fund; Young Investigator Award from the Children's Tumor Foundation +FX - The authors thank Dr Chris Atcherley for help with determining the absorbance properties of the fabricated lenses and Molly M. Ryan for assistance with analysis of proteomics data.M. M. Ibrahim and A. Patwardhan are co- first authors. M. M. Ibrahim and R. Khanna contributed equally. F. Porreca and R. Khanna are co- senior authors. This work was supported, in part, by a Career Development Award from the University of Arizona Health Sciences (to A. Patwardhan), and a Children's Tumor Foundation NF1 Synodos grant (to R. Khanna), and start- up seed funds (to M. M. Ibrahim and R. Khanna). A. Moutal was partially supported by a Young Investigator Award from the Children's Tumor Foundation. +PU - LIPPINCOTT WILLIAMS & WILKINS +PI - PHILADELPHIA +PA - TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA +SN - 0304-3959 +SN - 1872-6623 +J9 - PAIN +JI - Pain +DA - FEB +PY - 2017 +VL - 158 +IS - 2 +SP - 347 +EP - 360 +DO - 10.1097/j.pain.0000000000000767 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000397015500019 +N1 - Times Cited in Web of Science Core Collection: 75 +Total Times Cited: 83 +Cited Reference Count: 87 +ER - + +TY - JOUR +AU - Hill, RL +AU - Kulbe, JR +AU - Singh, IN +AU - Wang, JA +AU - Hall, ED +TI - Synaptic Mitochondria are More Susceptible to Traumatic Brain Injury-induced Oxidative Damage and Respiratory Dysfunction than Non-synaptic Mitochondria +T2 - NEUROSCIENCE +LA - English +KW - lipid peroxidation +KW - oxidative damage +KW - synaptic mitochondria +KW - non-synaptic mitochondria +KW - traumatic brain injury +KW - NEURONAL CYTOSKELETAL DEGRADATION +KW - LIPID-PEROXIDATION +KW - NITRIC-OXIDE +KW - MOUSE MODEL +KW - PROTEOMIC IDENTIFICATION +KW - PERMEABILITY TRANSITION +KW - CELL-DEATH +KW - ANTIOXIDANT THERAPIES +KW - AXONAL-TRANSPORT +KW - RAT-BRAIN +AB - Traumatic brain injury (TBI) results in mitochondrial dysfunction and induction of lipid peroxidation (LP). Lipid peroxidation-derived neurotoxic aldehydes such as 4-HNE and acrolein bind to mitochondrial proteins, inducing additional oxidative damage and further exacerbating mitochondrial dysfunction and LP. Mitochondria are heterogeneous, consisting of both synaptic and non-synaptic populations. Synaptic mitochondria are reported to be more vulnerable to injury; however, this is the first study to characterize the temporal profile of synaptic and non-synaptic mitochondria following TBI, including investigation of respiratory dysfunction and oxidative damage to mitochondria! proteins between 3 and 120 h following injury. These results indicate that synaptic mitochondria are indeed the more vulnerable population, showing both more rapid and severe impairments than non-synaptic mitochondria. By 24 h, synaptic respiration is significantly impaired compared to synaptic sham, whereas non-synaptic respiration does not decline significantly until 48 h. Decreases in respiration are associated with increases in oxidative damage to synaptic and non-synaptic mitochondria! proteins at 48 h and 72 h, respectively. These results indicate that the therapeutic window for mitochondria-targeted pharmacological neuroprotectants to prevent respiratory dysfunction is shorter for the more vulnerable synaptic mitochondria than for the non-synaptic population. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved. +AD - Univ Kentucky, Coll Med, Spinal Cord & Brain Injury Res Ctr SCoBIRC, 741 S Limestone St, Lexington, KY 40536 USA AD - Univ Kentucky, Dept Neurosci, Coll Med, 741 S Limestone St, Lexington, KY 40536 USA C3 - University of Kentucky C3 - University of Kentucky FU - Kentucky Spinal Cord & Head Injury Research Trust (KSCHIRT) [5R01 NS083405, 5R01 NS084857, 5P30 NS0512220, F30 NS096876] +FX - This work was supported by 5R01 NS083405, 5R01 NS084857, 5P30 NS0512220, F30 NS096876, and funding from the Kentucky Spinal Cord & Head Injury Research Trust (KSCHIRT). Rachel Hill was responsible for optimizing the isolation protocol for the non-synaptic and synaptic mitochondria from cortical tissue, performed all the experiments, and carried out most of the data analysis and overall organization and presentation of the data as well as statistical analysis, wrote most of the manuscript, designed graphs/figures and performed statistical analyses. Jacqueline Kulbe contributed to writing of the manuscript and some analysis of respiration and western blot data. Indrapal Singh assisted in mitochondrial respiratory assays and Juan Wang (Amy) assisted with animal work. Edward Hall supervised the experiments in his lab and contributed to the writing and organization of the manuscript. +PU - PERGAMON-ELSEVIER SCIENCE LTD +PI - OXFORD +PA - THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND +SN - 0306-4522 +SN - 1873-7544 +J9 - NEUROSCIENCE +JI - Neuroscience +DA - AUG 21 +PY - 2018 +VL - 386 +SP - 265 +EP - 283 +DO - 10.1016/j.neuroscience.2018.06.028 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000440325500022 +N1 - Times Cited in Web of Science Core Collection: 42 +Total Times Cited: 42 +Cited Reference Count: 147 +ER - + +TY - JOUR +AU - Rival, M +AU - Galoppin, M +AU - Thouvenot, E +TI - Biological Markers in Early Multiple Sclerosis: the Paved Way for Radiologically Isolated Syndrome +T2 - FRONTIERS IN IMMUNOLOGY +LA - English +KW - multiple sclerosis (MS) +KW - radiologically isolated syndrome (RIS) +KW - prognosis +KW - biomarkers +KW - personalized medicine +KW - Kappa free-light chain index (kFLC index) +KW - glial fibrillary acidic protein (GFAP) +KW - neurofilament-light chain (NfL) +KW - CLINICALLY ISOLATED SYNDROME +KW - NEUROFILAMENT LIGHT-CHAIN +KW - CEREBROSPINAL-FLUID +KW - PROGNOSTIC BIOMARKERS +KW - OLIGOCLONAL BANDS +KW - CONVERSION +KW - INFLAMMATION +KW - DISEASE +KW - CXCL13 +KW - CELLS +AB - Radiologically Isolated Syndrome (RIS) is characterized by MRI-typical brain lesions fulfilling the 2009 Okuda criteria, detected in patients without clinical conditions suggestive of MS. Half of all RIS patients convert to MS within 10 years. The individual course of the disease, however, is highly variable with 12% of RIS converting directly to progressive MS. Demographic and imaging markers have been associated with the risk of clinical MS in RIS: male sex, younger age, infra-tentorial, and spinal cord lesions on the index scan and gadolinium-enhancing lesions on index or follow-up scans. Although not considered as a distinct MS phenotype, RIS certainly shares common pathological features with early active and progressive MS. In this review, we specifically focus on biological markers that may help refine the risk stratification of clinical MS and disability for early treatment. Intrathecal B-cell activation with cerebrospinal fluid (CSF) oligoclonal bands, elevated kappa free light chains, and cytokine production is specific to MS, whereas neurofilament light chain (NfL) levels reflect disease activity associated with neuroaxonal injury. Specific microRNA profiles have been identified in RIS converters in both CSF and blood. CSF levels of chitinases and glial acidic fibrillary protein (GFAP) reflecting astrogliosis might help predict the evolution of RIS to progressive MS. Innovative genomic, proteomic, and metabolomic approaches have provided several new candidate biomarkers to be explored in RIS. Leveraging data from randomized controlled trials and large prospective RIS cohorts with extended follow-up to identify, as early as possible, biomarkers for predicting greater disease severity would be invaluable for counseling patients, managing treatment, and monitoring. +PU - FRONTIERS MEDIA SA +PI - LAUSANNE +PA - AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND +SN - 1664-3224 +J9 - FRONT IMMUNOL +JI - Front. Immunol. +DA - APR 27 +PY - 2022 +VL - 13 +C7 - 866092 +DO - 10.3389/fimmu.2022.866092 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000881911500001 +N1 - Times Cited in Web of Science Core Collection: 13 +Total Times Cited: 14 +Cited Reference Count: 93 +ER - + +TY - JOUR +AU - Gotovac, K +AU - Hajnsek, S +AU - Pasic, MB +AU - Pivac, N +AU - Boroveki, F +TI - Personalized Medicine in Neurodegenerative Diseases: How Far Away? +T2 - MOLECULAR DIAGNOSIS & THERAPY +LA - English +KW - MULTIPLE-SCLEROSIS +KW - BIOMARKERS +KW - MECHANISMS +KW - DISABILITY +KW - GENETICS +KW - GENOMICS +KW - GENES +KW - BETA +KW - MRI +AB - Neurodegenerative diseases are characterized by progressive dysfunction of the nervous system as a result of neuronal loss in the brain and spinal cord. Despite extensive research efforts aimed at development of new disease-modifying therapeutics, there is still no effective treatment to halt neurodegenerative processes. Thus, modification of current therapeutic and diagnostic research strategies is a goal of increasing urgency. The biggest limitation in neurodegenerative disease research is the lack of appropriate biomarkers. Discovery of universal biomarkers capable of diagnosing patients with neurodegenerative diseases, monitoring their response to therapy, and predicting disease progression seems to be a tall order. Instead, a combination of different methodologies in the discovery of biomarkers specific for each described aspect of the disease seems to be a more viable approach. Although application of personalized medicine in diagnosis and treatment of neurodegenerative diseases may seem far off, some recent developments, such as utilizing specific biological therapies in multiple sclerosis, microRNA profiling as a source of novel biomarkers in Parkinson's disease, or combination of neuroimaging and proteomic analyses in diagnosis of Alzheimer's disease patients, already point to the way clinical neurology may integrate new achievements in everyday practice. Combination of genomic, proteomic, glycomic, and metabolomic approaches may yield novel insights into molecular mechanisms of disease pathophysiology, which could then be integrated and translated into clinical neurology. Based on the developments during the past decade, it is feasible to predict that a personalized approach to treating neurological disorders will become more widely applicable in the coming years. +AD - Univ Zagreb, Sch Med, Univ Hosp Ctr Zagreb, Dept Funct Genom,Ctr Translat & Clin Res, Zagreb 41001, Croatia AD - Univ Hosp Ctr Zagreb, Dept Neurol, Zagreb, Croatia AD - Rudjer Boskovic Inst, Div Mol Med, Zagreb 10000, Croatia C3 - University of Zagreb C3 - UNIVERSITY ZAGREB HOSPITAL C3 - University of Zagreb C3 - UNIVERSITY ZAGREB HOSPITAL C3 - Rudjer Boskovic Institute FU - Parkinson's UK [K-1206] Funding Source: Medline +PU - ADIS INT LTD +PI - NORTHCOTE +PA - 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND +SN - 1177-1062 +SN - 1179-2000 +J9 - MOL DIAGN THER +JI - Mol. Diagn. Ther. +DA - FEB +PY - 2014 +VL - 18 +IS - 1 +SP - 17 +EP - 24 +DO - 10.1007/s40291-013-0058-z +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000330838400003 +N1 - Times Cited in Web of Science Core Collection: 18 +Total Times Cited: 20 +Cited Reference Count: 46 +ER - + +TY - JOUR +AU - Lin, X +AU - Wang, QS +AU - Cheng, Y +AU - Ji, JG +AU - Yu, LC +TI - Changes of protein expression profiles in the amygdala during the process of morphine-induced conditioned place preference in rats +T2 - BEHAVIOURAL BRAIN RESEARCH +LA - English +KW - Addiction +KW - Amygdala +KW - Conditioned place preference +KW - Proteomics +KW - UBIQUITIN-PROTEASOME ACTIVITY +KW - COCAINE-SEEKING BEHAVIOR +KW - PROTEOMIC ANALYSIS +KW - UP-REGULATION +KW - SIGNALING PATHWAY +KW - MEASURING REWARD +KW - DRUG-ADDICTION +KW - ERK PATHWAY +KW - SPINAL-CORD +KW - INVOLVEMENT +AB - Repeated exposures to addictive drugs result in persistent or even permanent expression changes of proteins in addiction-related brain regions, such as nucleus accumbens, hippocampus and prefrontal cortex while the changes of protein content in amygdala were seldom studied. Here we aimed to find the proteins involved in the process of morphine-induced conditioned place preference (CPP). The model of morphine-induced CPP was established in rats and the rat amygdala tissues were obtained in different stages of morphine-induced CPP: establishment group, extinction group, reinstatement group and saline group as a control. Two-dimensional electrophoresis (2-DE) was performed to analyze and compare the changes of protein expression profiles in the amygdala of rats during the process of morphine-induced CPP. There were eighty proteins with 1.3-fold changes in amygdala relative to saline group, most of which were down-regulated. These differentially expressed proteins were mainly involved in metabolism, structure, cell signaling pathway and ubiquitin-proteasome pathway. And we further used methods of reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting to confirm the results of proteomics. Mitosis activated protein kinase1 (MAPK1) was increased in the stages of extinction and reinstatement of morphine-induced CPP, while glial fibrillary acidic protein (GFAP) was decreased in the stage of extinction. Our results provide some proteins and cellular signaling pathways involved in the molecular mechanisms of opioid addiction in amygdala. (C) 2011 Elsevier B.V. All rights reserved. +AD - Peking Univ, State Key Lab Prot & Plant Gene Coll Life Sci, Beijing 100871, Peoples R China AD - Peking Univ, Neurobiol Lab, Beijing 100871, Peoples R China AD - Peking Univ, State Key Lab Biomembrane & Membrane Biotechnol, Coll Life Sci, Beijing 100871, Peoples R China C3 - Peking University C3 - Peking University C3 - Peking University FU - Ministry of Science and Technology of China [2009CB522002, 2010CB912203, 2011CB915504]; National Natural Science Foundation of China (NSFC) [30870802, 30711120564, 90919023, 30970652] +FX - This work was supported by grants from the National Program of Basic Research sponsored by the Ministry of Science and Technology of China (2009CB522002, 2010CB912203 and 2011CB915504) and the National Natural Science Foundation of China (NSFC Nos. 30870802; 30711120564; 90919023 and 30970652). +PU - ELSEVIER +PI - AMSTERDAM +PA - RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS +SN - 0166-4328 +SN - 1872-7549 +J9 - BEHAV BRAIN RES +JI - Behav. Brain Res. +DA - AUG 1 +PY - 2011 +VL - 221 +IS - 1 +SP - 197 +EP - 206 +DO - 10.1016/j.bbr.2011.03.002 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000290886200025 +N1 - Times Cited in Web of Science Core Collection: 23 +Total Times Cited: 25 +Cited Reference Count: 62 +ER - + +TY - JOUR +AU - Hu, WT +AU - Holtzman, DM +AU - Fagan, AM +AU - Shaw, LM +AU - Perrin, R +AU - Arnold, SE +AU - Grossman, M +AU - Xiong, CJ +AU - Craig-Schapiro, R +AU - Clark, CM +AU - Pickering, E +AU - Kuhn, M +AU - Chen, Y +AU - Van Deerlin, VM +AU - McCluskey, L +AU - Elman, L +AU - Karlawish, J +AU - Chen-Plotkin, A +AU - Hurtig, HI +AU - Siderowf, A +AU - Swenson, F +AU - Lee, VMY +AU - Morris, JC +AU - Trojanowski, JQ +AU - Soares, H +A1 - Alzheimer's Dis Neuroimaging Initi +TI - Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease +T2 - NEUROLOGY +LA - English +KW - FRONTOTEMPORAL LOBAR DEGENERATION +KW - NEUROIMAGING INITIATIVE SUBJECTS +KW - BRAIN NATRIURETIC PEPTIDE +KW - PANCREATIC-POLYPEPTIDE +KW - CLINICAL CHARACTERIZATION +KW - BIOMARKERS +KW - DIAGNOSIS +KW - DEMENTIA +KW - CLASSIFICATION +KW - PREDICTION +AB - Objectives: While plasma biomarkers have been proposed to aid in the clinical diagnosis of Alzheimer disease (AD), few biomarkers have been validated in independent patient cohorts. Here we aim to determine plasma biomarkers associated with AD in 2 independent cohorts and validate the findings in the multicenter Alzheimer's Disease Neuroimaging Initiative (ADNI). + Methods: Using a targeted proteomic approach, we measured levels of 190 plasma proteins and peptides in 600 participants from 2 independent centers (University of Pennsylvania, Philadelphia; Washington University, St. Louis, MO), and identified 17 analytes associated with the diagnosis of very mild dementia/mild cognitive impairment (MCI) or AD. Four analytes (apoE, B-type natriuretic peptide, C-reactive protein, pancreatic polypeptide) were also found to be altered in clinical MCI/AD in the ADNI cohort (n = 566). Regression analysis showed CSF A beta 42 levels and t-tau/A beta 42 ratios to correlate with the number of APOE4 alleles and plasma levels of B-type natriuretic peptide and pancreatic polypeptide. + Conclusion: Four plasma analytes were consistently associated with the diagnosis of very mild dementia/MCI/AD in 3 independent clinical cohorts. These plasma biomarkers may predict underlying AD through their association with CSF AD biomarkers, and the association between plasma and CSF amyloid biomarkers needs to be confirmed in a prospective study. Neurology (R) 2012;79:897-905 +AD - Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA AD - Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA AD - Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA AD - Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA AD - Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA AD - Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA AD - Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA AD - Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO USA AD - Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA AD - Avid Pharmaceut, Philadelphia, PA USA AD - Pfizer Global Res & Dev, Groton, CT USA AD - Bristol Myers Squibb Co, New London, CT USA C3 - University of Pennsylvania C3 - University of Pennsylvania C3 - University of Pennsylvania C3 - University of Pennsylvania C3 - University of Pennsylvania C3 - University of Pennsylvania C3 - Washington University (WUSTL) C3 - Washington University (WUSTL) C3 - Emory University C3 - Pfizer C3 - Pfizer USA C3 - Bristol-Myers Squibb FU - NIH [AG10124, AG17585, P50 AG05681, P01 AG03991, P01 AG026276, P30 NS057105, P30 AG010129, K01 AG030514, NIA P01 AG 09215-20, NIA P30 AG 10124-18, NIA PO1 AG 17586-10, NIA 1PO1 AG-19724-07, NIA 1 U01 AG 024904-05, NINDS P50 NS053488-02, NIA UO1 AG029213-01]; Penn-Pfizer Research Alliance at Penn; Pfizer; Charles F. and Joanne Knight Alzheimer Research Initiative at Washington University; Viretta Brady Discovery Fund; Emory University Center for Neurodegenerative Diseases at Emory University; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Abbott; AstraZeneca AB; Bayer Schering Pharma AG; Bristol-Myers Squibb; Eisai Global Clinical Development; Elan Corporation; Genentech; GE Healthcare; GlaxoSmithKline; Innogenetics; JohnsonJohnson; Eli Lilly and Co.; Medpace, Inc.; Merck and Co., Inc.; Novartis AG; Pfizer Inc; F. Hoffman-La Roche; Schering-Plough; Synarc, Inc.; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; US Food and Drug Administration; Dana Foundation; National Center for Research Resources (NCRR), NIH [UL1 RR024992]; National Center for Research Resources (NCRR), NIH Roadmap for Medical Research; AstraZeneca; Pfizer Inc.; Eli Lilly and Company; Forest Laboratories, Inc.; NIH; Cure Alzheimer's Fund; Fidelity Foundation; Morris K. Udall Parkinson's Disease Research Center of Excellence from NINDS [NS-053488]; health research grant by Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement [SAP4100027296, 2001-77]; Teva Neuroscience; Supernus Pharmaceuticals; Merck Serono; Takeda Pharmaceutical Company Ltd.; NIH NIA [NINDS P50 NS053488-02, NIA UO1 AG029213-01, PO1 AG 17586-10, PO1 AG-032953]; Marian S. Ware Alzheimer Program; Wyeth; Novartis; Avid Radiopharmaceuticals; NIA [P30AG036468]; [RC2NS069368]; [RC1AG035427]; National Institute on Aging [P01AG019724] Funding Source: NIH RePORTER +FX - This study has been supported by NIH grants AG10124, AG17585, and the Penn-Pfizer Research Alliance at Penn; a grant to Washington University from Pfizer, NIH grants P50 AG05681, P01 AG03991, P01 AG026276, P30 NS057105, and the Charles F. and Joanne Knight Alzheimer Research Initiative at Washington University; and the Viretta Brady Discovery Fund and Emory University Center for Neurodegenerative Diseases at Emory University. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson&Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the NIH (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. This publication was also made possible by Grant Number UL1 RR024992 from the National Center for Research Resources (NCRR), a component of the NIH, and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.W. Hu receives research support from the Viretta Brady Discovery Fund. D. Holtzman serves on scientific advisory boards for Satori Pharmaceuticals and EnVivo Pharmaceuticals; may accrue revenue on pending patents re: Methods for measuring the metabolism of neurally derived biomolecules in vivo; Use of anti-AB antibody to treat traumatic brain injury; Methods to treat Alzheimer's disease or other amyloid beta accumulation associated disorders; Humanized antibodies that sequester abeta peptide; Diagnostic for early stage Alzheimer's disease; and Predictive diagnostic for Alzheimer's disease; serves as a consultant to Merck Serono, Eli Lilly and Company, Takeda Pharmaceutical Company Limited, Abbott, Comentis, Inc., Eisai Inc., and AstraZeneca; is cofounder of and receives board of directors compensation from C2N Diagnostics LLC; receives research support from AstraZeneca, Pfizer Inc., Eli Lilly and Company, Elan Corporation, Forest Laboratories, Inc., the NIH, Cure Alzheimer's Fund, and Fidelity Foundation; has received compensation from Washington University from license revenue received for licensing of patent applications to C2N Diagnostics LLC; and may receive future royalty payments for Washington University licensing patents to C2N Diagnostics, LLC, and Eli Lilly and Company. A. Fagan serves on the speakers' bureau for the Alzheimer's Association. L. Shaw and R. Perrin report no disclosures. S. Arnold is a consultant to NIMH Geriatrics Branch and a member of the advisory board to Rush University Medical Center, was a compensated guest lecturer at Vanderbilt University, and was an expert witness to Cozen O'Connor and Reed-Smith. M. Grossman is a consultant to Allon Therapeutics, Forest Labs, and Pfizer Pharmaceuticals; a study section member at the NIH; a member of the editorial board for Wolters Kluwer Health; and a compensated lecturer at Sacred Heart Hospital. C. Xiong and R. Craig-Schapiro report no disclosures. C. Clark is deceased; disclosures are not included for this author. E. Pickering is an employee of Pfizer Global Research and Development. M. Kuhn is an employee of Pfizer Global Research and Development. Y. Chen is an employee of Pfizer Global Research and Development. V. Van Deerlin reports no disclosures. L. McCluskey was an expert witness to Gallagher & Rowan and Kilcoyne & Nesbitt. L. Elman, J. H. T. Karlawish, and A. Chen-Plotkin report no disclosures. H. Hurtig is a consultant to UpTo-Date. A. Siderowf is supported by a Morris K. Udall Parkinson's Disease Research Center of Excellence grant from NINDS (NS-053488), and has been supported by SAP4100027296, a health research grant awarded by the Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement under Act 2001-77. He has received consulting fees from Teva Neuroscience, Supernus Pharmaceuticals, Schering-Plough, and Merck Serono. He has received speaking honorarium from Teva Neuroscience. F. Swenson is an employee of Pfizer Global Research and Development. V. M.-Y. Lee has received funding for travel and honoraria from Takeda Pharmaceutical Company Ltd.; has received speaker honoraria from Pfizer Inc., BMS, and Merck; may accrue revenue on patents re: Modified avidin-biotin technique, Method of stabilizing microtubules to treat Alzheimer's disease, Method of detecting abnormally phosphorylated tau, Method of screening for Alzheimer's disease or disease associated with the accumulation of paired helical filaments, Compositions and methods for producing and using homogeneous neuronal cell transplants, Rat comprising straight filaments in its brain, Compositions and methods for producing and using homogeneous neuronal cell transplants to treat neurodegenerative disorders and brain and spinal cord injuries, Diagnostic methods for Alzheimer's disease by detection of multiple MRNAs, Methods and compositions for determining lipid peroxidation levels in oxidant stress syndromes and diseases, Compositions and methods for producing and using homogenous neuronal cell transplants, Method of identifying, diagnosing and treating alpha-synuclein positive neurodegenerative disorders, Mutation-specific functional impairments in distinct tau isoforms of hereditary frontotemporal dementia and parkinsonism linked to chromosome-17: genotype predicts phenotype, Microtubule stabilizing therapies for neurodegenerative disorders, and Treatment of Alzheimer's and related diseases with an antibody; and receives research support from the NIH NIA PO1 AG 17586-10, PO1 AG-032953, NINDS P50 NS053488-02, NIA UO1 AG029213-01; and from the Marian S. Ware Alzheimer Program. J. Morris serves on scientific advisory boards for AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., Merck Serono, Novartis, Pfizer Inc, Schering-Plough Corp., Eli Lilly and Company, Wyeth, and Elan Corporation; and receives research support from Elan Corporation, Wyeth, Eli Lilly and Company, Novartis, Pfizer Inc, Avid Radiopharmaceuticals, the NIH, and the Dana Foundation. J. Trojanowski has received funding for travel and honoraria from Takeda Pharmaceutical Company Ltd.; has received speaker honoraria from Pfizer Inc.; may accrue revenue on patents re: Modified avidin-biotin technique, Method of stabilizing microtubules to treat Alzheimer's disease, Method of detecting abnormally phosphorylated tau, Method of screening for Alzheimer's disease or disease associated with the accumulation of paired helical filaments, Compositions and methods for producing and using homogeneous neuronal cell transplants, Rat comprising straight filaments in its brain, Compositions and methods for producing and using homogeneous neuronal cell transplants to treat neurodegenerative disorders and brain and spinal cord injuries, Diagnostic methods for Alzheimer's disease by detection of multiple MRNAs, Methods and compositions for determining lipid peroxidation levels in oxidant stress syndromes and diseases, Compositions and methods for producing and using homogenous neuronal cell transplants, Method of identifying, diagnosing and treating alpha-synuclein positive neurodegenerative disorders, Mutation-specific functional impairments in distinct tau isoforms of hereditary frontotemporal dementia and parkinsonism linked to chromosome-17: genotype predicts phenotype, Microtubule stabilizing therapies for neurodegenerative disorders, and Treatment of Alzheimer's and related diseases with an antibody; and receives research support from the NIH (NIA P01 AG 09215-20 [PI], NIA P30 AG 10124-18 [PI], NIA PO1 AG 17586-10 [Project 4 Leader], NIA 1PO1 AG-19724-07 [Core C Leader], NIA 1 U01 AG 024904-05 [Co-PI Biomarker Core Laboratory], NINDS P50 NS053488-02 [PI], NIA UO1 AG029213-01 [Co-I]; RC2NS069368 [PI], RC1AG035427 [PI], and NIA P30AG036468 [PI]), and the Marian S. Ware Alzheimer Program. H. Soares is an employee of Bristol-Myers Squibb. Go to Neurology.org for full disclosures. +PU - LIPPINCOTT WILLIAMS & WILKINS +PI - PHILADELPHIA +PA - 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA +SN - 0028-3878 +J9 - NEUROLOGY +JI - Neurology +DA - AUG +PY - 2012 +VL - 79 +IS - 9 +SP - 897 +EP - 905 +DO - 10.1212/WNL.0b013e318266fa70 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000308406700018 +N1 - Times Cited in Web of Science Core Collection: 190 +Total Times Cited: 205 +Cited Reference Count: 40 +ER - + +TY - JOUR +AU - Rochín-Hernández, LJ +AU - Jiménez-Acosta, MA +AU - Ramírez-Reyes, L +AU - Figueroa-Corona, MD +AU - Sánchez-González, VJ +AU - Orozco-Barajas, M +AU - Meraz-Ríos, MA +TI - The Proteome Profile of Olfactory Ecto-Mesenchymal Stem Cells-Derived from Patients with Familial Alzheimer's Disease Reveals New Insights for AD Study +T2 - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES +LA - English +KW - proteome +KW - Alzheimer's disease +KW - Familial Alzheimer's disease +KW - PSEN1 +KW - A431E +KW - mesenchymal stem cells +KW - proteostasis +KW - olfactory +KW - neurodegeneration +KW - FAD +KW - SINGLE NUCLEOTIDE POLYMORPHISMS +KW - AMYLOID PRECURSOR PROTEIN +KW - GUANYLYL CYCLASE-C +KW - OXIDATIVE STRESS +KW - FUNCTIONAL-ANALYSIS +KW - PARKINSONS-DISEASE +KW - PHGDH EXPRESSION +KW - UP-REGULATION +KW - SPINAL-CORD +KW - NEURONS +AB - Alzheimer's disease (AD), the most common neurodegenerative disease and the first cause of dementia worldwide, has no effective treatment, and its pathological mechanisms are not yet fully understood. We conducted this study to explore the proteomic differences associated with Familial Alzheimer's Disease (FAD) in olfactory ecto-mesenchymal stem cells (MSCs) derived from PSEN1 (A431E) mutation carriers compared with healthy donors paired by age and gender through two label-free liquid chromatography-mass spectrometry approaches. The first analysis compared carrier 1 (patient with symptoms, P1) and its control (healthy donor, C1), and the second compared carrier 2 (patient with pre-symptoms, P2) with its respective control cells (C2) to evaluate whether the protein alterations presented in the symptomatic carrier were also present in the pre-symptom stages. Finally, we analyzed the differentially expressed proteins (DEPs) for biological and functional enrichment. These proteins showed impaired expression in a stage-dependent manner and are involved in energy metabolism, vesicle transport, actin cytoskeleton, cell proliferation, and proteostasis pathways, in line with previous AD reports. Our study is the first to conduct a proteomic analysis of MSCs from the Jalisco FAD patients in two stages of the disease (symptomatic and presymptomatic), showing these cells as a new and excellent in vitro model for future AD studies. +AD - Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Biomed Mol, Inst Politecn Nacl 2508, Mexico City 07360, Mexico AD - Ctr Invest & Estudios Avanzados, Lab Nacl Serv Expt LaNSE, Unidad Genom Prote & Metabol, Mexico City 07360, Mexico AD - Univ Guadalajara, Ctr Univ Altos, Tepatitlan De Morelos 47620, Mexico C3 - CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional C3 - Instituto Politecnico Nacional - Mexico C3 - CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional C3 - Universidad de Guadalajara FU - CONACYT [CF-2023-2206, 1008755, 854550] +FX - This research was funded by CONACYT, grant number CF-2023-2206-. Student's scholarships: 1008755 and 854550. +PU - MDPI +PI - BASEL +PA - ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND +SN - 1661-6596 +SN - 1422-0067 +J9 - INT J MOL SCI +JI - Int. J. Mol. Sci. +DA - AUG +PY - 2023 +VL - 24 +IS - 16 +C7 - 12606 +DO - 10.3390/ijms241612606 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001119055000001 +N1 - Times Cited in Web of Science Core Collection: 8 +Total Times Cited: 8 +Cited Reference Count: 185 +ER - + +TY - JOUR +AU - de Sousa, DMB +AU - Poupardin, R +AU - Villeda, SA +AU - Schroer, AB +AU - Fröhlich, T +AU - Frey, V +AU - Staffen, W +AU - Mrowetz, H +AU - Altendorfer, B +AU - Unger, MS +AU - Iglseder, B +AU - Paulweber, B +AU - Trinka, E +AU - Cadamuro, J +AU - Drerup, M +AU - Schallmoser, K +AU - Aigner, L +AU - Kniewallner, KM +TI - The platelet transcriptome and proteome in Alzheimer's disease and aging: an exploratory cross-sectional study +T2 - FRONTIERS IN MOLECULAR BIOSCIENCES +LA - English +KW - Alzheimer's disease +KW - aging +KW - platelets +KW - proteomics +KW - transcriptomics +KW - MILD COGNITIVE IMPAIRMENT +KW - MOUSE MODELS +KW - ACTIVATION +KW - AUTOPHAGY +KW - IMMUNOPROTEASOME +KW - BLOOD +KW - EXPRESSION +KW - RECEPTORS +KW - INCREASE +KW - DEMENTIA +AB - Introduction: Alzheimer's disease (AD) and aging are associated with platelet hyperactivity. However, the mechanisms underlying abnormal platelet function in AD and aging are yet poorly understood.Methods: To explore the molecular profile of AD and aged platelets, we investigated platelet activation (i.e., CD62P expression), proteome and transcriptome in AD patients, non-demented elderly, and young individuals as controls.Results: AD, aged and young individuals showed similar levels of platelet activation based on CD62P expression. However, AD and aged individuals had a proteomic signature suggestive of increased platelet activation compared with young controls. Transcriptomic profiling suggested the dysregulation of proteolytic machinery involved in regulating platelet function, particularly the ubiquitin-proteasome system in AD and autophagy in aging. The functional implication of these transcriptomic alterations remains unclear and requires further investigation.Discussion: Our data strengthen the evidence of enhanced platelet activation in aging and provide a first glimpse of the platelet transcriptomic changes occurring in AD. +AD - Paracelsus Med Univ, Inst Mol Regenerat Med, Salzburg, Austria AD - Paracelsus Med Univ, Spinal Cord Injury & Tissue Regenerat Ctr Salzburg, Salzburg, Austria AD - Paracelsus Med Univ, Expt & Clin Cell Therapy Inst, Salzburg, Austria AD - Univ Calif San Francisco, Dept Anat, San Francisco, CA USA AD - Ludwig Maximilian Univ Munich, Gene Ctr, Lab Funct Genome Anal LAFUGA, Munich, Germany AD - Paracelsus Med Univ, Dept Neurol, Christian Doppler Clin, Salzburg, Austria AD - Paracelsus Med Univ, St Johanns Univ Hosp, Dept Internal Med, Salzburg, Austria AD - UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth, Hlth Serv Res & Hlth Technol Assessment, Hall In Tirol, Austria AD - Paracelsus Med Univ, Christian Doppler Univ Hosp, Neurosci Inst, Salzburg, Austria AD - Ctr Cognit Neurosci Salzburg, Salzburg, Austria AD - Univ Hosp SALK, Dept Lab Med, Salzburg, Austria AD - Paracelsus Med Univ, Dept Urol, Salzburg, Austria AD - Paracelsus Med Univ, Dept Transfus Med, Salzburg, Austria AD - Austrian Cluster Tissue Regenerat, Vienna, Austria C3 - Paracelsus Private Medical University C3 - Paracelsus Private Medical University C3 - Paracelsus Private Medical University C3 - University of California System C3 - University of California San Francisco C3 - University of Munich C3 - Paracelsus Private Medical University C3 - Paracelsus Private Medical University C3 - UMIT - Private University for Health Sciences, Medical Informatics & Technology GmbH C3 - Paracelsus Private Medical University C3 - Paracelsus Private Medical University C3 - Paracelsus Private Medical University FU - PMU Rise Project (PMU-FFF) [R-14/04/097-KNI]; PMU postgraduate Students Support Program DISCITE! [D-19/01/008-BES] +FX - This work was supported by the PMU Rise Project (PMU-FFF) R-14/04/097-KNI and PMU postgraduate Students Support Program DISCITE! (D-19/01/008-BES). Funding bodies did not influence the design of the study, data collection, analysis and interpretation, or manuscript writing. +PU - FRONTIERS MEDIA SA +PI - LAUSANNE +PA - AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND +SN - 2296-889X +J9 - FRONT MOL BIOSCI +JI - Front. Mol. Biosci. +DA - JUN 30 +PY - 2023 +VL - 10 +C7 - 1196083 +DO - 10.3389/fmolb.2023.1196083 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001030372100001 +N1 - Times Cited in Web of Science Core Collection: 4 +Total Times Cited: 4 +Cited Reference Count: 92 +ER - + +TY - JOUR +AU - Leoni, E +AU - Bremang, M +AU - Mitra, V +AU - Zubiri, I +AU - Jung, S +AU - Lu, CH +AU - Adiutori, R +AU - Lombardi, V +AU - Russell, C +AU - Koncarevic, S +AU - Ward, M +AU - Pike, I +AU - Malaspina, A +TI - Combined Tissue-Fluid Proteomics to Unravel Phenotypic Variability in Amyotrophic Lateral Sclerosis +T2 - SCIENTIFIC REPORTS +LA - English +KW - SPINAL-CORD +KW - BIOMARKERS +KW - DISEASE +KW - PROGRESSION +KW - SURVIVAL +AB - The lack of biomarkers for early diagnosis, clinical stratification and to monitor treatment response has hampered the development of new therapies for amyotrophic lateral sclerosis (ALS), a clinically heterogeneous neurodegenerative disorder with a variable site of disease initiation and rate of progression. To identify new biomarkers and therapeutic targets, two separate proteomic workflows were applied to study the immunological response and the plasma/brain proteome in phenotypic variants of ALS. Conventional multiplex (TMT) proteomic analysis of peripheral blood mononuclear cells (PBMCs) was performed alongside a recently introduced method to profile neuronal-derived proteins in plasma using brain tissue-enhanced isobaric tagging (TMTcalibrator). The combined proteomic analysis allowed the detection of regulated proteins linked to ALS pathogenesis (RNA-binding protein FUS, superoxide dismutase Cu-Zn and neurofilaments light polypeptide) alongside newly identified candidate biomarkers (myosin-9, fructose-bisphosphate aldolase and plectin). In line with the proteomic results, orthogonal immunodetection showed changes in neurofilaments and ApoE in bulbar versus limb onset fast progressing ALS. Functional analysis of significantly regulated features showed enrichment of pathways involved in regulation of the immune response, Rho family GTPases, semaphorin and integrin signalling. Our cross-phenotype investigation of PBMCs and plasma/brain proteins provides a more sensitive biomarker exploratory platform than conventional case-control studies in a single matrix. The reported regulated proteins may represent novel biomarker candidates and potentially druggable targets. +AD - Proteome Sci R&D GmbH & Co KG, Altenhoferallee 3, D-60438 Frankfurt, Germany AD - Proteome Sci Plc, Hamilton House,Mabledon Pl, London WC1H 9BB, England AD - Queen Mary Univ London, Ctr Neurosci & Trauma, Blizard Inst, 4 Newark St, London E1 2AT, England C3 - University of London C3 - Queen Mary University London FU - MNDA [817-791]; Wellcome Trust [103208] +FX - The authors would like to thank all the ALS patients and their families for their kind support of this research project. We also acknowledge the contributions of Dr. Vadim Farztdinov, Proteome Sciences R&D GmbH & Co. KG in developing the FeaST bioinformatics tool applied in this study. We would like to acknowledge the MNDA for their support establishing the ALS biomarkers biobank and contributing with significant resources in the sample collection phase (Grant Number 817-791). We would like to acknowledge the Netherlands Brain Bank for providing the brain material. This study was supported by a Wellcome Trust Pathfinder Award (Grant Number 103208). +PU - NATURE PORTFOLIO +PI - BERLIN +PA - HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY +SN - 2045-2322 +J9 - SCI REP-UK +JI - Sci Rep +DA - MAR 14 +PY - 2019 +VL - 9 +C7 - 4478 +DO - 10.1038/s41598-019-40632-4 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000461151800062 +N1 - Times Cited in Web of Science Core Collection: 34 +Total Times Cited: 35 +Cited Reference Count: 38 +ER - + +TY - JOUR +AU - He, QR +AU - Man, LL +AU - Ji, YH +AU - Zhang, SQ +AU - Jiang, MR +AU - Ding, F +AU - Gu, XS +TI - Comparative Proteomic Analysis of Differentially Expressed Proteins between Peripheral Sensory and Motor Nerves +T2 - JOURNAL OF PROTEOME RESEARCH +LA - English +KW - iTRAQ +KW - proteomics +KW - motor nerve +KW - sensory nerve +KW - specificity +KW - peripheral nerve regeneration +KW - CELL-ADHESION MOLECULE +KW - SPINAL-CORD-INJURY +KW - NEURITE OUTGROWTH +KW - SCHWANN-CELLS +KW - CALCIUM-CHANNELS +KW - NERVOUS-SYSTEM +KW - STEM-CELLS +KW - L2/HNK-1 CARBOHYDRATE +KW - FUNCTIONAL RECOVERY +KW - SIGNALING PATHWAYS +AB - Peripheral sensory and motor nerves have different functions and different approaches to regeneration, especially their distinct ability to accurately reinervate terminal nerve pathways. To understand the molecular aspects underlying these differences, the proteomics technique by coupling isobaric tags for relative and absolute quantitation (iTRAQ) with online two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS) was used to investigate the protein profile of sensory and motor nerve samples from rats. A total of 1472 proteins were identified in either sensory or motor nerve. Of them, 100 proteins showed differential expressions between both nerves, and some of them were validated by quantitative real time RT-PCR, Western blot analysis, and immunohistochemistry. In the light of functional categorization, the differentially expressed proteins in sensory and motor nerves, belonging to a broad range of classes, were related to a diverse array of biological functions, which included cell adhesion, cytoskeleton, neuronal plasticity, neurotrophic activity, calcium-binding, signal transduction, transport, enzyme catalysis, lipid metabolism, DNA-binding, synaptosome function, actin-binding, ATP-binding, extracellular matrix, and commitment to other lineages. The relatively higher expressed proteins in either sensory or motor nerve were tentatively discussed in combination with their specific molecular characteristics. It is anticipated that the database generated in this study will provide a solid foundation for further comprehensive investigation of functional differences between sensory and motor nerves, including the specificity of their regeneration. +AD - Nantong Univ, Jiangsu Key Lab Neuroregenerat, Nantong 226001, Jiangsu, Peoples R China C3 - Nantong University FU - National Natural Foundation of China [81130080, 81171180] +FX - This study was supported by a project funded by the Priority Academic Program Development of Jiangsu High Education Institutions, National Natural Foundation of China (Grant Nos. 81130080 and 81171180). We thank Professor Jie Liu for assistance in manuscript preparation. +PU - AMER CHEMICAL SOC +PI - WASHINGTON +PA - 1155 16TH ST, NW, WASHINGTON, DC 20036 USA +SN - 1535-3893 +SN - 1535-3907 +J9 - J PROTEOME RES +JI - J. Proteome Res. +DA - JUN +PY - 2012 +VL - 11 +IS - 6 +SP - 3077 +EP - 3089 +DO - 10.1021/pr300186t +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000304682500003 +N1 - Times Cited in Web of Science Core Collection: 17 +Total Times Cited: 20 +Cited Reference Count: 79 +ER - + +TY - JOUR +AU - Akram, R +AU - Anwar, H +AU - Javed, MS +AU - Rasul, A +AU - Imran, A +AU - Malik, SA +AU - Raza, C +AU - Khan, IU +AU - Sajid, F +AU - Iman, T +AU - Sun, T +AU - Han, HS +AU - Hussain, G +TI - Axonal Regeneration: Underlying Molecular Mechanisms and Potential Therapeutic Targets +T2 - BIOMEDICINES +LA - English +KW - axonal regeneration +KW - nerve injury +KW - regeneration-associated genes +KW - neurotrophic factors +KW - cyclic adenosine monophosphate +KW - microRNAs +KW - PERIPHERAL-NERVE REGENERATION +KW - PROMOTES NEURITE OUTGROWTH +KW - RETINAL GANGLION-CELLS +KW - SPINAL-CORD-INJURY +KW - SIGNALING PATHWAY +KW - TENASCIN-C +KW - EXTRACELLULAR-MATRIX +KW - RHOA/RHO-KINASE +KW - GROWTH-CONTROL +KW - RAT MODEL +AB - Axons in the peripheral nervous system have the ability to repair themselves after damage, whereas axons in the central nervous system are unable to do so. A common and important characteristic of damage to the spinal cord, brain, and peripheral nerves is the disruption of axonal regrowth. Interestingly, intrinsic growth factors play a significant role in the axonal regeneration of injured nerves. Various factors such as proteomic profile, microtubule stability, ribosomal location, and signalling pathways mark a line between the central and peripheral axons' capacity for self-renewal. Unfortunately, glial scar development, myelin-associated inhibitor molecules, lack of neurotrophic factors, and inflammatory reactions are among the factors that restrict axonal regeneration. Molecular pathways such as cAMP, MAPK, JAK/STAT, ATF3/CREB, BMP/SMAD, AKT/mTORC1/p70S6K, PI3K/AKT, GSK-3 beta/CLASP, BDNF/Trk, Ras/ERK, integrin/FAK, RhoA/ROCK/LIMK, and POSTN/integrin are activated after nerve injury and are considered significant players in axonal regeneration. In addition to the aforementioned pathways, growth factors, microRNAs, and astrocytes are also commendable participants in regeneration. In this review, we discuss the detailed mechanism of each pathway along with key players that can be potentially valuable targets to help achieve quick axonal healing. We also identify the prospective targets that could help close knowledge gaps in the molecular pathways underlying regeneration and shed light on the creation of more powerful strategies to encourage axonal regeneration after nervous system injury. +AD - Govt Coll Univ, Fac Life Sci, Dept Physiol, Neurochem Biol & Genet Lab NGL, Faisalabad 38000, Pakistan AD - Sargodha Med Coll, Dept Physiol, Sargodha 40100, Pakistan AD - Govt Coll Univ, Fac Life Sci, Dept Zool, Faisalabad 38000, Pakistan AD - Govt Coll Univ, Dept Food Sci, Faisalabad 38000, Pakistan AD - Sargodha Med Coll, Dept Biochem, Sargodha 40100, Pakistan AD - Govt Coll Univ, Fac Chem & Life Sci, Dept Zool, Lahore 54000, Pakistan AD - Govt Coll Univ, Fac Pharmaceut Sci, Dept Pharmaceut, Faisalabad 38000, Pakistan AD - Huaqiao Univ, Ctr Precis Med, Sch Med, Xiamen 361021, Peoples R China AD - Huaqiao Univ, Sch Biomed Sci, Xiamen 361021, Peoples R China AD - Kyungpook Natl Univ, Clin Omics Inst, Sch Med, Dept Physiol, Daegu 41944, South Korea C3 - Government College University Faisalabad C3 - Government College University Faisalabad C3 - Government College University Faisalabad C3 - Government College University Lahore C3 - Government College University Faisalabad C3 - Huaqiao University C3 - Huaqiao University C3 - Kyungpook National University (KNU) PU - MDPI +PI - BASEL +PA - ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND +SN - 2227-9059 +J9 - BIOMEDICINES +JI - Biomedicines +DA - DEC +PY - 2022 +VL - 10 +IS - 12 +C7 - 3186 +DO - 10.3390/biomedicines10123186 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000900627800001 +N1 - Times Cited in Web of Science Core Collection: 33 +Total Times Cited: 35 +Cited Reference Count: 218 +ER - + +TY - JOUR +AU - Kumar, S +AU - Phaneuf, D +AU - Cordeau, P +AU - Boutej, H +AU - Kriz, J +AU - Julien, JP +TI - Induction of autophagy mitigates TDP-43 pathology and translational repression of neurofilament mRNAs in mouse models of ALS/FTD +T2 - MOLECULAR NEURODEGENERATION +LA - English +KW - MOTOR-NEURON DEATH +KW - LOBAR DEGENERATION +KW - WITHAFERIN +KW - PATHWAY +KW - DISEASE +KW - INHIBITION +KW - PATHOGENESIS +KW - MTOR +KW - GENE +AB - Background: TDP-43 proteinopathy is a pathological hallmark of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). So far, there is no therapy available for these neurodegenerative diseases. In addition, the impact of TDP-43 proteinopathy on neuronal translational profile also remains unknown. + Methods: Biochemical, immunohistology and assay-based studies were done with cell cultures and transgenic mice models. We also used Ribotag with microarray and proteomic analysis to determine the neuronal translational profile in the mice model of ALS/FTD. + Results: Here, we report that oral administration of a novel analog (IMS-088) of withaferin-A, an antagonist of nuclear factor kappa-B (NF-B) essential modulator (NEMO), induced autophagy and reduced TDP-43 proteinopathy in the brain and spinal cord of transgenic mice expressing human TDP-43 mutants, models of ALS/FTD. Treatment with IMS-088 ameliorated cognitive impairment, reduced gliosis in the brain of ALS/FTD mouse models. With the Ribotrap method, we investigated the impact of TDP-43 proteinopathy and IMS-088 treatment on the translation profile of neurons of one-year old hTDP-43(A315T) mice. TDP-43 proteinopathy caused translational dysregulation of specific mRNAs including translational suppression of neurofilament mRNAs resulting in 3 to 4-fold decrease in levels type IV neurofilament proteins. Oral administration of IMS-088 rescued the translational defects associated with TDP-43 proteinopathy and restored the synthesis of neurofilament proteins, which are essential for axon integrity and synaptic function. + Conclusions: Our study revealed that induction of autophagy reduces TDP-43 pathology and ameliorates the translational defect seen in mice models of ALS/FTD. Based on these results, we suggest IMS-088 and perhaps other inducers of autophagy should be considered as potential therapeutics for neurodegenerative disorders with TDP-43 proteinopathies. +AD - Univ Laval, CERVO Brain Res Ctr, Dept Psychiat & Neurosci, 2601 Chemin Canardiere, Quebec City, PQ G1J 2G3, Canada C3 - Laval University FU - Canadian Institutes of Health Research (CIHR); ALS Society of Canada; Brain Canada Foundation +FX - This work was funded by a grant from the Canadian Institutes of Health Research (CIHR), by a Hudson grant from the ALS Society of Canada and Brain Canada Foundation. +PU - BMC +PI - LONDON +PA - CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND +SN - 1750-1326 +J9 - MOL NEURODEGENER +JI - Mol. Neurodegener. +DA - JAN 7 +PY - 2021 +VL - 16 +IS - 1 +C7 - 1 +DO - 10.1186/s13024-020-00420-5 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000605971800001 +N1 - Times Cited in Web of Science Core Collection: 24 +Total Times Cited: 27 +Cited Reference Count: 47 +ER - + +TY - JOUR +AU - Han, MH +AU - Lin, CY +AU - Meng, SX +AU - Wang, XZ +TI - Proteomics Analysis Reveals Overlapping Functions of Clustered Protocadherins +T2 - MOLECULAR & CELLULAR PROTEOMICS +LA - English +KW - BLUE NATIVE ELECTROPHORESIS +KW - MEMBRANE-PROTEIN COMPLEXES +KW - CENTRAL-NERVOUS-SYSTEM +KW - ALPHA GENE-CLUSTER +KW - GAMMA-PROTOCADHERINS +KW - CELL-ADHESION +KW - POSTSYNAPTIC DENSITY +KW - COMBINATORIAL EXPRESSION +KW - CADHERIN SUPERFAMILY +KW - CYTOPLASMIC DOMAIN +AB - The three tandem-arrayed protocadherin (Pcdh) gene clusters, namely Pcdh-alpha, Pcdh-beta, and Pcdh-gamma, play important roles in the development of the vertebrate central nervous system. To gain insight into the molecular action of PCDHs, we performed a systematic proteomics analysis of PCDH-gamma-associated protein complexes. We identified a list of 154 non-redundant proteins in the PCDH-gamma complexes. This list includes nearly 30 members of clustered Pcdh-alpha, -beta, and -gamma families as core components of the complexes and additionally over 120 putative PCDH-associated proteins. We validated a selected subset of PCDH-gamma-associated proteins using specific antibodies. Analysis of the identities of PCDH-associated proteins showed that the majority of them overlap with the proteomic profile of postsynaptic density preparations. Further analysis of membrane protein complexes revealed that several validated PCDH-gamma-associated proteins exhibit reduced levels in Pcdh-gamma-deficient brain tissues. Therefore, PCDH-gamma s are required for the integrity of the complexes. However, the size of the overall complexes and the abundance of many other proteins remained unchanged, raising a possibility that PCDH-alpha s and PCDH-beta s might compensate for PCDH-gamma function in complex formation. As a test of this idea, RNA interference knockdown of both PCDH-alpha s and PCDH-gamma s showed that PCDHs have redundant functions in regulating neuronal survival in the chicken spinal cord. Taken together, our data provide evidence that clustered PCDHs coexist in large protein complexes and have overlapping functions during vertebrate neural development. Molecular & Cellular Proteomics 9: 71-83, 2010. +AD - Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA C3 - Northwestern University FU - Searle Funds at the Chicago Community Trust; National Institutes of Health [5R01NS051253] +FX - We thank Dr. L. Helseth for mass spectrometry data analysis, Dr. Y. Lu for advice on electroporation, Dr. C. C. Garner for anti-SAP102 antibody, and Dr. R. Holmgren for critical reading of the manuscript. Proteomics and informatics services were provided by the Chicago Biomedical Consortium/University of Illinois at Chicago Research Resources Center Proteomics and Informatics Services Facility, which was established by a grant from The Searle Funds at the Chicago Community Trust to the Chicago Biomedical Consortium.This work was supported, in whole or in part, by National Institutes of Health Grant 5R01NS051253 to (X. W.). +PU - AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC +PI - BETHESDA +PA - 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA +SN - 1535-9476 +SN - 1535-9484 +J9 - MOL CELL PROTEOMICS +JI - Mol. Cell. Proteomics +DA - JAN +PY - 2010 +VL - 9 +IS - 1 +SP - 71 +EP - 83 +DO - 10.1074/mcp.M900343-MCP200 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000275505900006 +N1 - Times Cited in Web of Science Core Collection: 56 +Total Times Cited: 69 +Cited Reference Count: 59 +ER - + +TY - JOUR +AU - Magliocca, G +AU - Esposito, E +AU - Tufano, M +AU - Piccialli, I +AU - Rubino, V +AU - Tedeschi, V +AU - Sisalli, MJ +AU - Carriero, F +AU - Ruggiero, G +AU - Secondo, A +AU - Annunziato, L +AU - Scorziello, A +AU - Pannaccione, A +TI - Involvement of KV3.4 Channel in Parkinson's Disease: A Key Player in the Control of Midbrain and Striatum Differential Vulnerability during Disease Progression? +T2 - ANTIOXIDANTS +LA - English +KW - Parkinson's disease +KW - K(V)3.4 channel +KW - A53T mice +KW - ROS +KW - calcium dyshomeostasis +KW - astrocyte +KW - SUBSTANTIA-NIGRA NEURONS +KW - KAPPA-B ACTIVATION +KW - POTASSIUM CHANNELS +KW - UP-REGULATION +KW - KV CHANNELS +KW - K+ CHANNELS +KW - SPINAL-CORD +KW - IN-VITRO +KW - SUBUNIT +KW - CELLS +AB - Parkinson's disease (PD), the second most common neurodegenerative disease in the elderly, is characterized by selective loss of dopaminergic neurons and accumulation of alpha-synuclein (alpha-syn), mitochondrial dysfunction, Ca2+ dyshomeostasis, and neuroinflammation. Since current treatments for PD merely address symptoms, there is an urgent need to identify the PD pathophysiological mechanisms to develop better therapies. Increasing evidence has identified K(V)3.4, a ROS-sensitive K-V channel carrying fast-inactivating currents, as a potential therapeutic target against neurodegeneration. In fact, it has been hypothesized that K(V)3.4 channels could play a role in PD etiopathogenesis, controlling astrocytic activation and detrimental pathways in A53T mice, a well-known model of familial PD. Here, we showed that the A53T midbrain, primarily involved in the initial phase of PD pathogenesis, displayed an early upregulation of the K(V)3.4 channel at 4 months, followed by its reduction at 12 months, compared with age-matched WT. On the other hand, in the A53T striatum, the expression of K(V)3.4 remained high at 12 months, decreasing thereafter, in 16-month-old mice. The proteomic profile highlighted a different detrimental phenotype in A53T brain areas. In fact, the A53T striatum and midbrain differently expressed neuroprotective/detrimental pathways, with the variation of astrocytic p27(kip1), XIAP, and Smac/DIABLO expression. Of note, a switch from protective to detrimental phenotype was characterized by the upregulation of Smac/DIABLO and downregulation of p27(kip1) and XIAP. This occurred earlier in the A53T midbrain, at 12 months, compared with the striatum proteomic profile. In accordance, an upregulation of Smac/DIABLO and a downregulation of p27(kip1) occurred in the A53T striatum only at 16 months, showing the slowest involvement of this brain area. Of interest, HIF-1 alpha overexpression was associated with the detrimental profile in midbrain and its major vulnerability. At the cellular level, patch-clamp recordings revealed that primary A53T striatum astrocytes showed hyperpolarized resting membrane potentials and lower firing frequency associated with K(V)3.4 ROS-dependent hyperactivity, whereas primary A53T midbrain astrocytes displayed a depolarized resting membrane potential accompanied by a slight increase of K(V)3.4 currents. Accordingly, intracellular Ca2+ homeostasis was significantly altered in A53T midbrain astrocytes, in which the ER Ca2+ level was lower than in A53T striatum astrocytes and the respective littermate controls. Collectively, these results suggest that the early K(V)3.4 overexpression and ROS-dependent hyperactivation in astrocytes could take part in the different vulnerabilities of midbrain and striatum, highlighting astrocytic K(V)3.4 as a possible new therapeutic target in PD. +AD - Federico II Univ Naples, Sch Med, Dept Neurosci Reprod & Dent Sci, Div Pharmacol, Via Pansini 5, I-80131 Naples, Italy AD - Univ Naples Federico II, Dept Translat Med Sci, I-80131 Naples, Italy AD - Univ Basilicata, Dept Sci, I-85100 Potenza, Italy AD - IRCCS SYNLAB SDN, Via Emanuele Gianturco 113, I-80143 Naples, Italy C3 - University of Naples Federico II C3 - University of Naples Federico II C3 - University of Basilicata C3 - Italfarmaco FU - Progetto FRA; Ministry of University and Research (MUR); National Recovery and Resilience Plan (NRRP) [PE0000006]; PRIN (PROGETTI DI RICERCA DI RILEVANTE INTERESSE NAZIONALE) [2022ZTKFXS, 1553 11.10.2022]; [CdA_54_2020_FRA] +FX - This research was funded by Progetto FRA (CdA_54_2020_FRA to A.P.); funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006); PRIN (PROGETTI DI RICERCA DI RILEVANTE INTERESSE NAZIONALE) Prot. 2022ZTKFXS to A.P.; PRIN-Bando 2022 PNRR Prot. P2022P88K5 to Agnese Secondo; A multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022) to Agnese Secondo and A.P. +PU - MDPI +PI - BASEL +PA - ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND +SN - 2076-3921 +J9 - ANTIOXIDANTS-BASEL +JI - Antioxidants +DA - AUG +PY - 2024 +VL - 13 +IS - 8 +C7 - 999 +DO - 10.3390/antiox13080999 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001307363200001 +N1 - Times Cited in Web of Science Core Collection: 0 +Total Times Cited: 0 +Cited Reference Count: 67 +ER - + +TY - JOUR +AU - Huttunen, KM +AU - Terasaki, T +AU - Urtti, A +AU - Montaser, AB +AU - Uchida, Y +TI - Pharmacoproteomics of Brain Barrier Transporters and Substrate Design for the Brain Targeted Drug Delivery +T2 - PHARMACEUTICAL RESEARCH +LA - English +KW - blood-arachnoid barrier +KW - blood-brain barrier +KW - molecular dynamics simulations +KW - pharmacoproteomics +KW - prodrug +KW - AMINO-ACID TRANSPORTER +KW - 1 UTILIZING PRODRUGS +KW - MDR1 P-GLYCOPROTEIN +KW - CEREBROSPINAL-FLUID +KW - ORGANIC ANION +KW - CHOROID-PLEXUS +KW - HUMAN-EQUILIBRATIVE-NUCLEOSIDE-TRANSPORTER-1 HENT1 +KW - MITOCHONDRIAL TOXICITY +KW - ABSOLUTE PROTEOMICS +KW - QUANTITATIVE ATLAS +AB - One of the major reasons why central nervous system (CNS)-drug development has been challenging in the past, is the barriers that prevent substances entering from the blood circulation into the brain. These barriers include the blood-brain barrier (BBB), blood-spinal cord barrier (BSCB), blood-cerebrospinal fluid barrier (BCSFB), and blood-arachnoid barrier (BAB), and they differ from each other in their transporter protein expression and function as well as among the species. The quantitative expression profiles of the transporters in the CNS-barriers have been recently revealed, and in this review, it is described how they affect the pharmacokinetics of compounds and how these expression differences can be taken into account in the prediction of brain drug disposition in humans, an approach called pharmacoproteomics. In recent years, also structural biology and computational resources have progressed remarkably, enabling a detailed understanding of the dynamic processes of transporters. Molecular dynamics simulations (MDS) are currently used commonly to reveal the conformational changes of the transporters and to find the interactions between the substrates and the protein during the binding, translocation in the transporter cavity, and release of the substrate on the other side of the membrane. The computational advancements have also aided in the rational design of transporter-utilizing compounds, including prodrugs that can be actively transported without losing potency towards the pharmacological target. In this review, the state-of-art of these approaches will be also discussed to give insights into the transporter-mediated drug delivery to the CNS. +AD - Univ Eastern Finland, Fac Hlth Sci, Sch Pharm, POB 1627, FI-70211 Kuopio, Finland AD - Tohoku Univ, Grad Sch Pharmaceut Sci, Aoba Ku, 6-3 Aoba, Sendai, Miyagi 9808578, Japan C3 - University of Eastern Finland C3 - Tohoku University FU - Academy of Finland GeneCellNano Flagship; Academy of Finland PROFI6; Sigrid Juselius Foundation; Academy of Finland; Paivikki and Sakari Sohlberg Foundation; Grants-in-Aid for Scientific Research [22H04798, 22H05393, 21K19365, 20H03399, 20H04690, 20H05495] Funding Source: KAKEN +FX - This study is supported in part by Academy of Finland GeneCellNano Flagship and PROFI6. Tetsuya Terasaki acknowledges to the Sigrid Juselius Foundation for supporting visiting professor grant and Kristiina Huttunen would like to thank Dr. Santosh K. Adla and Arun Tonduru for the graphical design of the figures and Academy of Finland, Paivikki and Sakari Sohlberg Foundation, and Sigrid Juselius Foundation for supporting transporter proteomic studies by project funds. The authors declare no competing interest. +PU - SPRINGER/PLENUM PUBLISHERS +PI - NEW YORK +PA - 233 SPRING ST, NEW YORK, NY 10013 USA +SN - 0724-8741 +SN - 1573-904X +J9 - PHARM RES-DORDR +JI - Pharm. Res. +DA - JUL +PY - 2022 +VL - 39 +IS - 7 +SP - 1363 +EP - 1392 +DO - 10.1007/s11095-022-03193-2 +C6 - MAR 2022 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000765711100001 +N1 - Times Cited in Web of Science Core Collection: 22 +Total Times Cited: 23 +Cited Reference Count: 163 +ER - + +TY - JOUR +AU - Teixeira, FG +AU - Panchalingam, KM +AU - Assunçao-Silva, R +AU - Serra, SC +AU - Mendes-Pinheiro, B +AU - Patrício, P +AU - Jung, S +AU - Anjo, SI +AU - Manadas, B +AU - Pinto, L +AU - Sousa, N +AU - Behie, LA +AU - Salgado, AJ +TI - Modulation of the Mesenchymal Stem Cell Secretome Using Computer-Controlled Bioreactors: Impact on Neuronal Cell Proliferation, Survival and Differentiation +T2 - SCIENTIFIC REPORTS +LA - English +KW - NERVE GROWTH-FACTOR +KW - CYSTATIN-C +KW - ADULT NEUROGENESIS +KW - NEURAL PROGENITORS +KW - OXIDATIVE STRESS +KW - NEWBORN NEURONS +KW - UMBILICAL-CORD +KW - IN-VITRO +KW - BRAIN +KW - GALECTIN-1 +AB - In recent years it has been shown that the therapeutic benefits of human mesenchymal stem/stromal cells (hMSCs) in the Central Nervous System (CNS) are mainly attributed to their secretome. The implementation of computer-controlled suspension bioreactors has shown to be a viable route for the expansion of these cells to large numbers. As hMSCs actively respond to their culture environment, there is the hypothesis that one can modulate its secretome through their use. Herein, we present data indicating that the use of computer-controlled suspension bioreactors enhanced the neuroregulatory profile of hMSCs secretome. Indeed, higher levels of in vitro neuronal differentiation and NOTCH1 expression in human neural progenitor cells (hNPCs) were observed when these cells were incubated with the secretome of dynamically cultured hMSCs. A similar trend was also observed in the hippocampal dentate gyrus (DG) of rat brains where, upon injection, an enhanced neuronal and astrocytic survival and differentiation, was observed. Proteomic analysis also revealed that the dynamic culturing of hMSCs increased the secretion of several neuroregulatory molecules and miRNAs present in hMSCs secretome. In summary, the appropriate use of dynamic culture conditions can represent an important asset for the development of future neuro-regenerative strategies involving the use of hMSCs secretome. +AD - Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga, Portugal AD - PT Govt Associate Lab, ICVS 3Bs, Braga, Portugal AD - Univ Calgary, Schulich Sch Engn, PPRF, Calgary, AB, Canada AD - Univ Coimbra, CNC Ctr Neurosci & Cell Biol, P-3000 Coimbra, Portugal AD - Univ Coimbra, Fac Sci & Technol, Coimbra, Portugal AD - Biocant Biotechnol Innovat Ctr, Cantanhede, Portugal C3 - Universidade do Minho C3 - University of Calgary C3 - Universidade de Coimbra C3 - Universidade de Coimbra FU - Portuguese Foundation for Science and Technology (FCT); IF Development Grant; Canada Research Chair in Biomedical Engineering; SSE Postdoctoral Fellowship; "COMPETE Programa Operacional Factores de Competitividade", QREN [PEst-C/SAU/LA0001/2013-2014]; European Union (FEDER - Fundo Europeu de Desenvolvimento Regional); National Mass Spectrometry Network (RNEM) [REDE/1506/REM/2005]; [SFRH/69637/2010]; [SFRH/BD/81495/2011]; Fundação para a Ciência e a Tecnologia [SFRH/BD/81495/2011] Funding Source: FCT +FX - We acknowledge the financial support of the Portuguese Foundation for Science and Technology (FCT) for a Ciencia 2007 program and IF Development Grant (AJS), a pre-doctoral fellowship to FGT (SFRH/69637/2010) and a PhD fellowship to SA (SFRH/BD/81495/2011), a Canada Research Chair in Biomedical Engineering (LAB) and a SSE Postdoctoral Fellowship (KMP). Premios Santa Casa Neurociencias - Prize Melo e Castro for Spinal Cord Injury Research. PEst-C/SAU/LA0001/2013-2014. Co-funded by "COMPETE Programa Operacional Factores de Competitividade", QREN, the European Union (FEDER - Fundo Europeu de Desenvolvimento Regional) and by The National Mass Spectrometry Network (RNEM) under the contract REDE/1506/REM/2005. +PU - NATURE PORTFOLIO +PI - BERLIN +PA - HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY +SN - 2045-2322 +J9 - SCI REP-UK +JI - Sci Rep +DA - JUN 15 +PY - 2016 +VL - 6 +C7 - 27791 +DO - 10.1038/srep27791 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000384559600001 +N1 - Times Cited in Web of Science Core Collection: 91 +Total Times Cited: 104 +Cited Reference Count: 57 +ER - + +TY - JOUR +AU - Sapienza, S +AU - Tedeschi, V +AU - Apicella, B +AU - Pannaccione, A +AU - Russo, C +AU - Sisalli, MJ +AU - Magliocca, G +AU - Loffredo, S +AU - Secondo, A +TI - Ultrafine particulate matter pollution and dysfunction of endoplasmic reticulum Ca2+ store: A pathomechanism shared with amyotrophic lateral sclerosis motor neurons? +T2 - ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY +LA - English +KW - Air pollution +KW - Carbon PM +KW - [Ca2+]i homeostasis +KW - ER-stress +KW - Neurotoxicity +KW - SOCE +KW - AIR-POLLUTION +KW - CALCIUM +KW - PARTICLES +KW - HEALTH +KW - RISK +KW - SIZE +KW - NEURODEGENERATION +KW - EXPOSURE +KW - STRESS +KW - ENTRY +AB - Increased risk of neurodegenerative diseases has been envisaged for air pollution exposure. On the other hand, environmental risk factors, including air pollution, have been suggested for Amyotrophic Lateral Sclerosis (ALS) pathomechanism. Therefore, the neurotoxicity of ultrafine particulate matter (PM0.1) (PM < 0.1 mu m size) and its sub-20 nm nanoparticle fraction (NP20) has been investigated in motor neuronal-like cells and primary cortical neurons, mainly affected in ALS. The present data showed that PM0.1 and NP20 exposure induced endoplasmic reticulum (ER) stress, as occurred in cortex and spinal cord of ALS mice carrying G93A mutation in SOD1 gene. Furthermore, NSC-34 motor neuronal-like cells exposed to PM0.1 and NP20 shared the same proteomic profile on some apoptotic factors with motor neurons treated with the L-BMAA, a neurotoxin inducing Amyotrophic Lateral Sclerosis/Parkinson-Dementia Complex (ALS/PDC). Of note ER stress induced by PM0.1 and NP20 in motor neurons was associated to pathological changes in ER morphology and dramatic reduction of organellar Ca2+ level through the dysregulation of the Ca2+-pumps SERCA2 and SERCA3, the Ca2+-sensor STIM1, and the Ca2+-release channels RyR3 and IP3R3. Furthermore, the mechanism deputed to ER Ca2+ refilling (e.g. the so called store operated calcium entry-SOCE) and the relative currents ICRAC were also altered by PM0.1 and NP20 exposure. Additionally, these carbonaceous particles caused the exacerbation of L-BMAA-induced ER stress and Caspase-9 activation. In conclusion, this study shows that PM0.1 and NP20 induced the aberrant expression of ER proteins leading to dysmorphic ER, organellar Ca2+ dysfunction, ER stress and neurotoxicity, providing putative correlations with the neurodegenerative process occurring in ALS. +AD - Univ Naples Federico II, Dept Neurosci Reprod & Odontostomatol Sci, I-80131 Naples, Italy AD - CNR, Ist Sci & Tecnol Energia & Mobil Sostenibili STEMS, I-80125 Naples, Italy AD - Univ Naples Federico II, Dept Translat Med Sci, I-80131 Naples, Italy AD - Univ Naples Federico II, Ctr Basic & Clin Immunol Res CISI, WAO Ctr Excellence, I-80131 Naples, Italy C3 - University of Naples Federico II C3 - Consiglio Nazionale delle Ricerche (CNR) C3 - University of Naples Federico II C3 - University of Naples Federico II FU - Progetto FRA [CdA_54_2020_FRA]; #NEXTGENERATIONEU (NGEU); Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP) [PE0000006, 1553]; Progetto Fondazione Roche per la Ricerca Indipendente 2021 [57254] +FX - This work was supported by Progetto FRA (CdA_54_2020_FRA to A. S.), #NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006) - A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022) to A.S. and A.P., and Progetto Fondazione Roche per la Ricerca Indipendente 2021 (57254) to V.T. +PU - ACADEMIC PRESS INC ELSEVIER SCIENCE +PI - SAN DIEGO +PA - 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA +SN - 0147-6513 +SN - 1090-2414 +J9 - ECOTOX ENVIRON SAFE +JI - Ecotox. Environ. Safe. +DA - MAR 15 +PY - 2024 +VL - 273 +C7 - 116104 +DO - 10.1016/j.ecoenv.2024.116104 +C6 - FEB 2024 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001200553300001 +N1 - Times Cited in Web of Science Core Collection: 3 +Total Times Cited: 3 +Cited Reference Count: 51 +ER - + +TY - JOUR +AU - Serra, SC +AU - Costa, JC +AU - Assunçao-Silva, RC +AU - Teixeira, FG +AU - Silva, NA +AU - Anjo, SI +AU - Manadas, B +AU - Gimble, JM +AU - Behie, LA +AU - Salgado, AJ +TI - Influence of passage number on the impact of the secretome of adipose tissue stem cells on neural survival, neurodifferentiation and axonal growth +T2 - BIOCHIMIE +LA - English +KW - Secretome +KW - Adipose tissue stem cells +KW - Central nervous system +KW - Differentiation +KW - Axonal growth +KW - Proteomics +KW - PROMOTES NEURITE OUTGROWTH +KW - EPITHELIUM-DERIVED FACTOR +KW - DISEASE PROTEIN DJ-1 +KW - NEURONAL DIFFERENTIATION +KW - PARKINSONS-DISEASE +KW - SIGNALING PATHWAY +KW - STROMAL CELLS +KW - IN-VITRO +KW - MESENCHYMAL PROGENITORS +KW - HIPPOCAMPAL-NEURONS +AB - Mesenchymal stem cells (MSCs), and within them adipose tissue derived stem cells (ASCs), have been shown to have therapeutic effects on central nervous system (CNS) cell populations. Such effects have been mostly attributed to soluble factors, as well as vesicles, present in their secretome. Yet, little is known about the impact that MSC passaging might have in the secretion therapeutic profile. Our aim was to show how human ASCs (hASCs) passage number influences the effect of their secretome in neuronal survival, differentiation and axonal growth. For this purpose, post-natal rat hippocampal primary cultures, human neural progenitor cell (hNPCs) cultures and dorsal root ganglia (DRGs) explants were incubated with secretome, collected as conditioned media (CM), obtained from hASCs in P3, P6, P9 and P12. Results showed no differences when comparing percentages of MAP-2 positive cells (a mature neuronal marker) in neuronal cultures or hNPCs, after incubation with hASCs secretome from different passages. The same was observed regarding DRG neurite outgrowth. In order to characterize the secretomes obtained from different passages, a proteomic analysis was performed, revealing that its composition did not vary significantly with passage number P3 to P12. Results allowed us to identify several key proteins, such as pigment epithelium derived factor (PEDF), DJ-1, interleucin-6 (IL-6) and galectin, all of which have already proven to play neuroprotective and neurodifferentiating roles. Proteins that promote neurite outgrowth were also found present, such as semaphorin 7A and glypican-1. We conclude that cellular passaging does not influence significantly hASCs's secretome properties especially their ability to support post-natal neuronal survival, induce neurodifferentiation and promote axonal growth. (C) 2018 Published by Elsevier B.V. +AD - Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga, Portugal AD - ICVS 3Bs PT Govt Associated Lab, Braga, Portugal AD - Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Coimbra, Portugal AD - Univ Coimbra, Fac Sci & Technol, Coimbra, Portugal AD - Tulane Univ, Ctr Stem Cell Res & Regenerat Med, New Orleans, LA 70118 USA AD - Univ Calgary, Schulich Sch Engn, PPRF, Calgary, AB, Canada C3 - Universidade do Minho C3 - Universidade de Coimbra C3 - Universidade de Coimbra C3 - Tulane University C3 - University of Calgary FU - Premios Santa Casa Neurociencias - Prize Melo e Castro for Spinal Cord Injury Research [MC-17-2013, MC-04-2017]; Portuguese Foundation for Science and Technology through an IF Development Grant [IF/00111/2013]; FCT [TUBITAK/0007/2014]; Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) [NORTE-01-0145-FEDER-000013]; FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE); Foundation for Science and Technology (FCT) [POCI-01-0145-FEDER-007038, PTDC/NEU-NMC/0205/2012, POCI-01-0145-FEDER-016428, SAICTPAC/0010/2015]; National Mass Spectrometry Network (RNEM) [LISBOA-01-0145-FEDER-402-022125, ROTEIRO/0028/2013]; European Social Fund through the POCH - Programa Operacional do Capital Humano; FCT; [SFRH/BD/81495/2011]; Fundação para a Ciência e a Tecnologia [SFRH/BD/81495/2011] Funding Source: FCT +FX - The authors acknowledge the financial support by Premios Santa Casa Neurociencias - Prize Melo e Castro for Spinal Cord Injury Research (MC-17-2013 and MC-04-2017); Portuguese Foundation for Science and Technology through an IF Development Grant to A. J. Salgado (IF/00111/2013). Canada Research Chair in Biomedical Engineering (LAB). This work was funded by national funds through FCT under the scope of grant reference TUBITAK/0007/2014. This article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has also been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the projects POCI-01-0145-FEDER-007038, PTDC/NEU-NMC/0205/2012, POCI-01-0145-FEDER-016428 (ref.: SAICTPAC/0010/2015); and by The National Mass Spectrometry Network (RNEM) under the contract LISBOA-01-0145-FEDER-402-022125 (ref.: ROTEIRO/0028/2013). SIA was supported by PhD fellowship SFRH/BD/81495/2011, co-financed by the European Social Fund through the POCH - Programa Operacional do Capital Humano and national funds via FCT. +PU - ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER +PI - ISSY-LES-MOULINEAUX +PA - 65 RUE CAMILLE DESMOULINS, CS50083, 92442 ISSY-LES-MOULINEAUX, FRANCE +SN - 0300-9084 +SN - 1638-6183 +J9 - BIOCHIMIE +JI - Biochimie +DA - DEC +PY - 2018 +VL - 155 +SP - 119 +EP - 128 +DO - 10.1016/j.biochi.2018.09.012 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000450903000014 +N1 - Times Cited in Web of Science Core Collection: 18 +Total Times Cited: 21 +Cited Reference Count: 74 +ER - + +TY - JOUR +AU - Lonser, RR +AU - Vortmeyer, AO +AU - Butman, JA +AU - Glasker, S +AU - Finn, MA +AU - Ammerman, JM +AU - Merrill, MJ +AU - Edwards, NA +AU - Zhuang, ZP +AU - Oldfield, EH +TI - Edema is a precursor to central nervous system peritumoral cyst formation +T2 - ANNALS OF NEUROLOGY +LA - English +KW - ENDOTHELIAL GROWTH-FACTOR +KW - VASCULAR-PERMEABILITY FACTOR +KW - SURGICAL-MANAGEMENT +KW - TUMOR-TISSUE +KW - BRAIN-TUMORS +KW - FACTOR VEGF +KW - HEMANGIOBLASTOMAS +KW - RECEPTOR +KW - PATHOGENESIS +KW - EXPRESSION +AB - Despite the common occurrence and frequent clinical effects of peritumoral cysts in the central nervous system (CNS), the mechanism underlying their development and evolution is not understood. Because they commonly produce peritumoral cysts and because serial magnetic resonance imaging (MRI) is obtained in von Hippel-Lindau disease patients, hemangioblastomas provide an opportunity to examine the pathophysiology of CNS peritumoral cyst formation. Serial MRI was correlated with the clinical findings in 16 von Hippel-Lindau disease patients with 22 CNS hemangioblastomas (11 spinal cord; 11 cerebellar) that were associated with the appearance and evolution of peritumoral cysts. Hemangioblastoma-associated cyst wall histomorphological analysis was performed on postmortem tissues from three von Hippel-Lindau disease patients (not in the clinical series). Comparative proteomic profiling was performed on peritumoral cyst fluid and serum. Vascular endothelial growth factor levels were determined in peritumoral cysts. MRI dearly showed peritumoral edema that developed and slowly and progressively evolved into enlarging hemangioblastoma-associated cysts in all tumors (mean follow-up, 130 +/- 38 months; mean +/- standard deviation). Postcontrast MRI demonstrated convective leakage of gadolinium into cysts. Mean time required for edema to evolve into a cyst was 36 +/- 23 months (range, 8-72 months). Thirteen (59%) hemangioblastoma-cysts became symptomatic (mean time to symptom formation after cyst development, 35 +/- 32 months; range, 3-102 months) and required resection. Protein profiles of cyst fluid and serum were similar. Mean cyst fluid vascular endothelial growth factor concentration was 1.5ng/ml (range, 0-5.4ng/ml). Histology of the cyst walls was consistent with reactive gliosis. CNS peritumoral cyst formation is initiated by increased tumor vascular permeability, increased interstitial pressure in the tumor, and plasma extravasation with convective distribution into the surrounding tissue. When the delivery of plasma from the tumor exceeds the capacity of the surrounding tissue to absorb the extravasated fluid, edema (with its associated increased interstitial pressure) and subsequent cyst formation occur. +AD - Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA AD - NIH, Neuroradiol Sect, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA C3 - National Institutes of Health (NIH) - USA C3 - NIH National Institute of Neurological Disorders & Stroke (NINDS) C3 - National Institutes of Health (NIH) - USA PU - WILEY +PI - HOBOKEN +PA - 111 RIVER ST, HOBOKEN 07030-5774, NJ USA +SN - 0364-5134 +SN - 1531-8249 +J9 - ANN NEUROL +JI - Ann. Neurol. +DA - SEP +PY - 2005 +VL - 58 +IS - 3 +SP - 392 +EP - 399 +DO - 10.1002/ana.20584 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000231679200008 +N1 - Times Cited in Web of Science Core Collection: 70 +Total Times Cited: 72 +Cited Reference Count: 31 +ER - + +TY - JOUR +AU - Yu, Y +AU - Tang, J +AU - Su, JJ +AU - Cui, JH +AU - Xie, X +AU - Chen, FL +TI - Integrative Analysis of MicroRNAome, Transcriptome, and Proteome during the Limb Regeneration of Cynops orientalis +T2 - JOURNAL OF PROTEOME RESEARCH +LA - English +KW - Cynops orientalis +KW - microRNA +KW - stage-specific regulation +KW - limb regeneration +KW - SPINAL-CORD REGENERATION +KW - POTENTIAL REGULATORS +KW - CELL-PROLIFERATION +KW - GENE-EXPRESSION +KW - CANCER-CELLS +KW - TAIL +KW - SALAMANDER +KW - MATRIX +KW - MIRNA +KW - DIFFERENTIATION +AB - Salamanders completely regenerate their limbs after amputation. Thus, these animals are unique models to investigate the mechanisms modulating regeneration in vertebrates. To investigate the influence of microRNAs (miRNAs) on newt limb regeneration, the miRNAs and mRNAs were simultaneously profiled using Illumina HiSeq 2500 System during limb regeneration of Cynops orientalis at 3, 7, 14, 30 and 42 days postamputation. A total of 203 miRNAs and 4230 mRNAs were identified to be differentially expressed. Together with the proteomic data obtained from our previous study, integrative analysis of multiple profiling data sets was performed to construct an interaction network of differentially expressed miRNAs, mRNAs and proteins. Results of GO and KEGG analyses showed that the differentially expressed miRNA targets were mainly directed to cytoskeletal remodeling and carbohydrate metabolism. The stage-specific regulation of miRNAs on their targets was analyzed by hierarchical clustering analysis and validated by qRT-PCR The negative regulation of miR-223 and miR-133a on their targets was tested by performing dual luciferase reporter assay. The integration analysis will provide a powerful tool to identify the regulatory mechanisms of miRNAs and their targets. The results may have implications in understanding the complex mechanisms underlying newt limb regeneration. +AD - Northwest Univ, Coll Life Sci, Lab Tissue Engn, Xian 710069, Shaanxi, Peoples R China AD - Prov Key Lab Biotechnol Shaanxi, Xian 710069, Shaanxi, Peoples R China AD - Minist Educ, Key Lab Resource Biol & Biotechnol Western China, Xian 710069, Shaanxi, Peoples R China AD - Shaanxi Inst Zool, 88 Xingqing Rd, Xian 710032, Shaanxi, Peoples R China C3 - Northwest University Xi'an FU - National Natural Science Foundation of China [31771055, 31670996] +FX - We would like to thank LC Science for analysis of deep sequencing data. This work was supported by the National Natural Science Foundation of China [grant numbers 31771055, 31670996]. +PU - AMER CHEMICAL SOC +PI - WASHINGTON +PA - 1155 16TH ST, NW, WASHINGTON, DC 20036 USA +SN - 1535-3893 +SN - 1535-3907 +J9 - J PROTEOME RES +JI - J. Proteome Res. +DA - MAR +PY - 2019 +VL - 18 +IS - 3 +SP - 1088 +EP - 1098 +DO - 10.1021/acs.jproteome.8b00778 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000460491800025 +N1 - Times Cited in Web of Science Core Collection: 7 +Total Times Cited: 9 +Cited Reference Count: 86 +ER - + +TY - JOUR +AU - Nardo, G +AU - Pozzi, S +AU - Pignataro, M +AU - Lauranzano, E +AU - Spano, G +AU - Garbelli, S +AU - Mantovani, S +AU - Marinou, K +AU - Papetti, L +AU - Monteforte, M +AU - Torri, V +AU - Paris, L +AU - Bazzoni, G +AU - Lunetta, C +AU - Corbo, M +AU - Mora, G +AU - Bendotti, C +AU - Bonetto, V +TI - Amyotrophic Lateral Sclerosis Multiprotein Biomarkers in Peripheral Blood Mononuclear Cells +T2 - PLOS ONE +LA - English +KW - ENDOPLASMIC-RETICULUM STRESS +KW - UNFOLDED PROTEIN RESPONSE +KW - INCREASED 3-NITROTYROSINE +KW - PROTEOMIC ANALYSIS +KW - OXIDATIVE DAMAGE +KW - SKELETAL-MUSCLE +KW - EXTEND SURVIVAL +KW - MOTOR-NEURONS +KW - SPORADIC ALS +KW - EXPRESSION +AB - Background: Amyotrophic lateral sclerosis (ALS) is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments. + Methodology/Principal Findings: We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC), a panel of protein biomarkers that are closely associated with ALS. Validations and a longitudinal study were performed by immunoassays on a selected number of proteins. The same proteins were also measured in PBMC and spinal cord of a G93A SOD1 transgenic rat model. We identified combinations of protein biomarkers that can distinguish, with high discriminatory power, ALS patients from healthy controls (98%), and from patients with neurological disorders that may resemble ALS (91%), between two levels of disease severity (90%), and a number of translational biomarkers, that link responses between human and animal model. We demonstrated that TDP-43, cyclophilin A and ERp57 associate with disease progression in a longitudinal study. Moreover, the protein profile changes detected in peripheral blood mononuclear cells of ALS patients are suggestive of possible intracellular pathogenic mechanisms such as endoplasmic reticulum stress, nitrative stress, disturbances in redox regulation and RNA processing. + Conclusions/Significance: Our results indicate that PBMC multiprotein biomarkers could contribute to determine amyotrophic lateral sclerosis diagnosis, differential diagnosis, disease severity and progression, and may help to elucidate pathogenic mechanisms. +AD - Dulbecco Telethon Inst, Milan, Italy AD - Mario Negri Inst Pharmacol Res, Dept Mol Biochem & Pharmacol, Milan, Italy AD - Mario Negri Inst Pharmacol Res, Dept Neurosci, Milan, Italy AD - Ist Ricovero & Cura Carattere Sci IRCCS Fdn Salva, Pavia, Italy AD - IRCCS Fdn Salvato Maugeri, Natl Inst Occupat Safety & Prevent ISPESL, Res Ctr, Pavia, Italy AD - Mario Negri Inst Pharmacol Res, Dept Oncol, Milan, Italy AD - Osped Niguarda Ca Granda, NEuroMuscular Omnictr NEMO, Milan, Italy AD - IRCCS Fdn Salvatore Maugeri, Milan, Italy C3 - Fondazione Telethon C3 - Dulbecco Telethon Institute (DTI) C3 - Istituto di Ricerche Farmacologiche Mario Negri IRCCS C3 - Istituto di Ricerche Farmacologiche Mario Negri IRCCS C3 - Istituti Clinici Scientifici Maugeri IRCCS C3 - Istituto di Ricerche Farmacologiche Mario Negri IRCCS C3 - Ospedale Niguarda Ca' Granda C3 - IRCCS Ca Granda Ospedale Maggiore Policlinico C3 - Istituti Clinici Scientifici Maugeri IRCCS FU - Telethon Foundation [S01010, TCR08002]; Cariplo Foundation; Compagnia San Paolo Foundation; Fondazione Aldo e Cele Dacco per la ricerca scientifica; Vialli and Mauro Foundation for Research and Sport; European Community [FP7/2007-2013, 259867] +FX - This work was supported by Telethon Foundation (S01010 and TCR08002 to V. B.), Cariplo Foundation (to V.B. and C.B.), Compagnia San Paolo Foundation (to V.B.), Fondazione Aldo e Cele Dacco per la ricerca scientifica (to V. B.), Vialli and Mauro Foundation for Research and Sport (to S.P. and V.B.), and the European Community's Seventh Framework Programme (FP7/2007-2013) under the Health Cooperation Programme, grant agreement no 259867 (to V.B. and C.B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. +PU - PUBLIC LIBRARY SCIENCE +PI - SAN FRANCISCO +PA - 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA +SN - 1932-6203 +J9 - PLOS ONE +JI - PLoS One +DA - OCT 5 +PY - 2011 +VL - 6 +IS - 10 +C7 - e25545 +DO - 10.1371/journal.pone.0025545 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000295966900033 +N1 - Times Cited in Web of Science Core Collection: 108 +Total Times Cited: 111 +Cited Reference Count: 56 +ER - + +TY - JOUR +AU - Skalnikova, H +AU - Vodicka, P +AU - Gadher, SJ +AU - Kovarova, H +TI - Proteomics of neural stem cells +T2 - EXPERT REVIEW OF PROTEOMICS +LA - English +KW - cell-based regenerative and reparative therapy +KW - conditioned media +KW - differentiation +KW - neural stem cell +KW - neurodegenerative disease +KW - proteomics +KW - CENTRAL-NERVOUS-SYSTEM +KW - PROGENITOR CELLS +KW - HUNTINGTONS-DISEASE +KW - SUBVENTRICULAR ZONE +KW - SPINAL-CORD +KW - 2-DIMENSIONAL ELECTROPHORESIS +KW - NEURODEGENERATIVE DISEASES +KW - DIRECTED DIFFERENTIATION +KW - NEURONAL DIFFERENTIATION +KW - REGENERATION STRATEGIES +AB - The isolation of neural stem cells from fetal and adult mammalian CNS and the demonstration of functional neurogenesis in adult CNS have offered perspectives for treatment of many devastating hereditary and acquired neurological diseases. Due to this enormous potential, neural stem cells are a subject of extensive molecular profiling studies with a search for new markers and regulatory pathways governing their self-renewal as opposed to differentiation. Several in-depth proteomic studies have been conducted on primary or immortalized cultures of neural stem cells and neural progenitor cells, and yet more remains to be done. Additionally, neurons and glial cells have been obtained from embryonic stem cells and mesenchymal stem cells, and proteins associated with the differentiation process have been characterized to a certain degree with a view to further investigations. This review summarizes recent findings relevant to the proteomics of neural stem cells and discusses major proteins significantly regulated during neural stem cell differentiation with a view to their future use in cell-based regenerative and reparative therapy. +AD - Acad Sci Czech Republ, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic AD - Joint Proteome Lab, Prague 14220, Czech Republic AD - Beckman Coulter Int SA, CH-1260 Nyon, Switzerland C3 - Czech Academy of Sciences C3 - Institute of Animal Physiology & Genetics of the Czech Academy of Sciences C3 - Beckman Coulter Inc. PU - TAYLOR & FRANCIS LTD +PI - ABINGDON +PA - 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND +SN - 1478-9450 +SN - 1744-8387 +J9 - EXPERT REV PROTEOMIC +JI - Expert Rev. Proteomics +DA - APR +PY - 2008 +VL - 5 +IS - 2 +SP - 175 +EP - 186 +DO - 10.1586/14789450.5.2.175 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000256740400005 +N1 - Times Cited in Web of Science Core Collection: 16 +Total Times Cited: 18 +Cited Reference Count: 83 +ER - + +TY - JOUR +AU - Wieloch, T +AU - Nikolich, K +TI - Mechanisms of neural plasticity following brain injury +T2 - CURRENT OPINION IN NEUROBIOLOGY +LA - English +KW - FOCAL CEREBRAL-ISCHEMIA +KW - CENTRAL-NERVOUS-SYSTEM +KW - MARROW STROMAL CELLS +KW - SPINAL-CORD-INJURY +KW - FUNCTIONAL RECOVERY +KW - STEM-CELLS +KW - ENVIRONMENTAL ENRICHMENT +KW - GENE-EXPRESSION +KW - STROKE RECOVERY +KW - ADULT RATS +AB - Brain insults cause rapid cell death, and a disruption of functional circuits, in the affected regions. As the injured tissue recovers from events associated with cell death, regenerative processes are activated that over months lead to a certain degree of functional recovery. Factors produced by new neurons and glia, axonal sprouting of surviving neurons, and new synapse formation help to re-establish some of the lost functions. The timing and location of such events is crucial in the success of the regenerative process. Comprehensive gene expression profiling and proteomic analyses have enabled a deeper molecular and cellular mechanistic understanding of post-injury brain regeneration. These new mechanistic insights are aiding the design of novel therapeutic modalities that enhance regeneration. +AD - Lund Univ, Wallenberg Neurosci Ctr, Lab Expt Brain Res, S-22185 Lund, Sweden AD - Stanford Univ, Sch Med, Inst Neurosci, Stanford, CA 94305 USA AD - AGH Therapeut Inc, San Francisco, CA 94080 USA C3 - Lund University C3 - Stanford University PU - CURRENT BIOLOGY LTD +PI - LONDON +PA - 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND +SN - 0959-4388 +SN - 1873-6882 +J9 - CURR OPIN NEUROBIOL +JI - Curr. Opin. Neurobiol. +DA - JUN +PY - 2006 +VL - 16 +IS - 3 +SP - 258 +EP - 264 +DO - 10.1016/j.conb.2006.05.011 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000239163000003 +N1 - Times Cited in Web of Science Core Collection: 265 +Total Times Cited: 328 +Cited Reference Count: 63 +ER - + +TY - JOUR +AU - Eastlake, K +AU - Lamb, WDB +AU - Luis, J +AU - Khaw, PT +AU - Jayaram, H +AU - Limb, GA +TI - Prospects for the application of Muller glia and their derivatives in retinal regenerative therapies +T2 - PROGRESS IN RETINAL AND EYE RESEARCH +LA - English +KW - Muller glia +KW - Neural retina +KW - Stem cells +KW - Regeneration +KW - Neuroprotection +KW - PLURIPOTENT STEM-CELLS +KW - CHONDROITIN SULFATE PROTEOGLYCANS +KW - VESICLES PROMOTE NEUROPROTECTION +KW - SPINAL-CORD-INJURY +KW - GANGLION-CELLS +KW - NEUROTROPHIC FACTOR +KW - OPTIC-NERVE +KW - IN-VITRO +KW - NEURAL REGENERATION +KW - AXONAL REGENERATION +AB - Neural cell death is the main feature of all retinal degenerative disorders that lead to blindness. Despite therapeutic advances, progression of retinal disease cannot always be prevented, and once neuronal cell damage occurs, visual loss cannot be reversed. Recent research in the stem cell field, and the identification of Muller glia with stem cell characteristics in the human eye, have provided hope for the use of these cells in retinal therapies to restore vision. Muller glial cells, which are the major structural cells of the retina, play a very important role in retinal homeostasis during health and disease. They are responsible for the spontaneous retinal regeneration observed in zebrafish and lower vertebrates during early postnatal life, and despite the presence of Muller glia with stem cell characteristics in the adult mammalian retina, there is no evidence that they promote regeneration in humans. Like many other stem cells and neurons derived from pluripotent stem cells, Muller glia with stem cell potential do not differentiate into retinal neurons or integrate into the retina when transplanted into the vitreous of experimental animals with retinal degeneration. However, despite their lack of integration, grafted Muller glia have been shown to induce partial restoration of visual function in spontaneous or induced experimental models of photoreceptor or retinal ganglion cell damage. This improvement in visual function observed after Muller cell transplantation has been ascribed to the release of neuroprotective factors that promote the repair and survival of damaged neurons. Due to the development and availability of pluripotent stem cell lines for therapeutic uses, derivation of Muller cells from retinal organoids formed by iPSC and ESC has provided more realistic prospects for the application of these cells to retinal therapies. Several opportunities for research in the regenerative field have also been unlocked in recent years due to a better understanding of the genomic and proteomic profiles of the developing and regenerating retina in zebrafish, providing the basis for further studies of the human retina. In addition, the increased interest on the nature and function of cellular organelle release and the characterization of molecular components of exosomes released by Muller glia, may help us to design new approaches that could be applied to the development of more effective treatments for retinal degenerative diseases. +AD - Moorfields Eye Hosp, NIHR Biomed Res Ctr, London, England AD - UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England C3 - University of London C3 - University College London C3 - Moorfields Eye Hospital NHS Foundation Trust C3 - University of London C3 - University College London FU - Medical Research Council (MRC) [MR/K008722/1]; Fight for Sight, UK; Moorfields Eye Charity, UK; NIHR Biomedical Research Centre at Moorfields Eye Hospital; UCL Institute of Ophthalmology, London, UK +FX - The study was supported by the Medical Research Council (MRC grant Refs. MR/K008722/1); Fight for Sight (through two private donations), UK; Moorfields Eye Charity, UK; and NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK. The views expressed are those of the authors and not of the NIHR. +PU - PERGAMON-ELSEVIER SCIENCE LTD +PI - OXFORD +PA - THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND +SN - 1350-9462 +SN - 1873-1635 +J9 - PROG RETIN EYE RES +JI - Prog. Retin. Eye Res. +DA - NOV +PY - 2021 +VL - 85 +C7 - 100970 +DO - 10.1016/j.preteyeres.2021.100970 +C6 - NOV 2021 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000720124200002 +N1 - Times Cited in Web of Science Core Collection: 41 +Total Times Cited: 46 +Cited Reference Count: 256 +ER - + +TY - JOUR +AU - Gonzalez, H +AU - Ottervald, J +AU - Nilsson, KC +AU - Sjögren, N +AU - Miliotis, T +AU - Von Bahr, H +AU - Khademi, M +AU - Eriksson, B +AU - Kjellström, S +AU - Vegvari, A +AU - Harris, R +AU - Marko-Varga, G +AU - Borg, K +AU - Nilsson, J +AU - Laurell, T +AU - Olsson, T +AU - Franzén, B +TI - Identification of novel candidate protein biomarkers for the post-polio syndrome - implications for diagnosis, neurodegeneration and neuroinflammation +T2 - JOURNAL OF PROTEOMICS +LA - English +KW - Post-polio syndrome +KW - Pathophysiology +KW - CSF +KW - Proteomics +KW - Biomarkers +KW - Diagnosis +KW - ALPHA-AMIDATING MONOOXYGENASE +KW - CENTRAL-NERVOUS-SYSTEM +KW - CEREBROSPINAL-FLUID +KW - ALZHEIMERS-DISEASE +KW - SPINAL-CORD +KW - MULTIPLE-SCLEROSIS +KW - INTRAVENOUS IMMUNOGLOBULIN +KW - PRIOR POLIOMYELITIS +KW - CYTOKINE PRODUCTION +KW - HUMAN KALLIKREIN-6 +AB - Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, a condition known as post-polio syndrome (PPS). The condition affects 20-60% of previous polio patients, making it one of the most common causes of neurological deficits worldwide. The underlying pathogenesis is not fully understood and accurate diagnosis is not feasible. Herein we investigated whether it was possible to identify proteomic profile aberrations in the cerebrospinal fluid (CSF) of PPS patients. + CSF from 15 patients with well-defined PPS were analyzed for protein expression profiles. The results were compared to data obtained from nine healthy controls and 34 patients with other non-inflammatory diseases which served as negative controls. In addition, 17 samples from persons with secondary progressive multiple sclerosis (SPMS) were added as relevant age-matched references for the PPS samples. + The CSF of persons with PPS displayed a disease-specific and highly predictive (P=0.0017) differential expression of five distinct proteins: gelsolin, hemopexin, peptidylglycine alpha-amidating monooxygenase, glutathione synthetase and kallikrein 6, respectively, in comparison with the control groups. An independent ELISA confirmed the increase of kallikrein 6. + We suggest that these five proteins should be further evaluated as candidate biomarkers for the diagnosis and development of new therapies for PPS patients. (C) 2008 Elsevier B.V. All rights reserved. +AD - Karolinska Hosp, CMM, Neuroimmunol Unit, Dept Clin Neurosci, S-17176 Stockholm, Sweden AD - Karolinska Hosp, Danderyd Hosp, Dept Clin Sci, Div Rehabil Med, S-17176 Stockholm, Sweden AD - AstraZeneca R&D Sodertalje, Mol Pharmacol, Sodertalje, Sweden AD - AstraZeneca R&D Sodertalje, Local Discovery, Dis Biol, Sodertalje, Sweden AD - AstraZeneca R&D Sodertalje, Biostat, Sodertalje, Sweden AD - AstraZeneca R&D, Local Discovery, Biosci, Molndal, Sweden AD - AstraZeneca R&D Sodertalje, BioPR&D, Sodertalje, Sweden AD - AstraZeneca R&D, Local Discovery, Biol Sci, Lund, Sweden AD - Lund Tech Univ, Lund, Sweden C3 - Karolinska Institutet C3 - Karolinska University Hospital C3 - Karolinska Institutet C3 - Karolinska University Hospital C3 - Danderyds Hospital C3 - AstraZeneca C3 - AstraZeneca C3 - AstraZeneca C3 - AstraZeneca C3 - AstraZeneca C3 - AstraZeneca C3 - Lund University FU - Gustaf V foundation; Swedish medical research council; Swedish research council; Gustav V foundation +FX - The proteomics have been done at AstraZeneca R&D, the clinical parts, and sample collections have been supported by grants from the Gustaf V foundation and the Swedish medical research council. The Swedish research council, Gustav V foundation. Hugh Salter and Jenny Flygare for reviewing the manuscript. Jon D Randall for technical assistance and support regarding the PDQuest software. Lisbet Broman for her excellent coordination of the clinical data. +PU - ELSEVIER SCIENCE BV +PI - AMSTERDAM +PA - PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS +SN - 1874-3919 +SN - 1876-7737 +J9 - J PROTEOMICS +JI - J. Proteomics +DA - JAN 30 +PY - 2009 +VL - 71 +IS - 6 +SP - 670 +EP - 681 +DO - 10.1016/j.jprot.2008.11.014 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000263426500010 +N1 - Times Cited in Web of Science Core Collection: 39 +Total Times Cited: 43 +Cited Reference Count: 61 +ER - + +TY - JOUR +AU - Jha, MK +AU - Kim, JH +AU - Suk, K +TI - Proteome of brain glia: The molecular basis of diverse glial phenotypes +T2 - PROTEOMICS +LA - English +KW - Biomarker +KW - Biomedicine +KW - CNS +KW - Glia +KW - Proteome +KW - Therapeutic target +KW - CENTRAL-NERVOUS-SYSTEM +KW - SPINAL-CORD-INJURY +KW - CEREBROSPINAL-FLUID PROTEOME +KW - MILD COGNITIVE IMPAIRMENT +KW - EXTRACELLULAR-MATRIX PROTEINS +KW - NEUROPATHIC PAIN MODEL +KW - SRC-FAMILY KINASES +KW - ALZHEIMERS-DISEASE +KW - MICROGLIAL ACTIVATION +KW - MULTIPLE-SCLEROSIS +AB - Several different types of nonneuronal glial cells with diverse phenotypes are present in the CNS, and all have distinct indispensible functions. Although glial cells primarily provide neurons with metabolic and structural support in the healthy brain, they may switch phenotype from a resting to a reactive state in response to pathological insults. Furthermore, this reactive gliosis is an invariant feature of the pathogeneses of CNS maladies. The glial proteome serves as a signature of glial phenotype, and not only executes physiological functions, but also acts as a molecular mediator of the reactive glial phenotype. The glial proteome is also involved in intra- and intercellular communications as exemplified by glia-glia and neuron-glia interactions. The utilization of authoritative proteomic tools and the bioinformatic analyses have helped to profile the brain glial proteome and explore the molecular mechanisms of diverse glial phenotypes. Furthermore, technologic innovations have equipped the field of glioproteomics with refined tools for studies of the expression, interaction, and function of glial proteins in the healthy and in the diseased CNS. Glioproteomics is expected to contribute to the elucidation of the molecular mechanisms of CNS pathophysiology and to the discovery of biomarkers and theragnostic targets in CNS disorders. +AD - Kyungpook Natl Univ, Dept Pharmacol, Sch Med, Brain Sci & Engn Inst, Taegu 700422, South Korea C3 - Kyungpook National University (KNU) FU - National Research Foundation (NRF); Ministry of Education, Science and Technology (MEST) of the Korean government [2012-0009328]; Bio & Medical Technology Development Program of the NRF; MEST [2012M3A9B6055414]; Korean Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A111345] +FX - This work was supported by the National Research Foundation (NRF) grants funded by the Ministry of Education, Science and Technology (MEST) of the Korean government (2012-0009328), and by the Bio & Medical Technology Development Program of the NRF funded by the MEST (2012M3A9B6055414). This study was also supported by a grant from the Korean Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A111345). +PU - WILEY +PI - HOBOKEN +PA - 111 RIVER ST, HOBOKEN 07030-5774, NJ USA +SN - 1615-9853 +SN - 1615-9861 +J9 - PROTEOMICS +JI - Proteomics +DA - MAR +PY - 2014 +VL - 14 +IS - 4-5 +SP - 378 +EP - 398 +DO - 10.1002/pmic.201300236 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000332341200005 +N1 - Times Cited in Web of Science Core Collection: 16 +Total Times Cited: 19 +Cited Reference Count: 272 +ER - + +TY - JOUR +AU - Holland, A +AU - Schmitt-John, T +AU - Dowling, P +AU - Meleady, P +AU - Henry, M +AU - Clynes, M +AU - Ohlendieck, K +TI - Intricate effects of primary motor neuronopathy on contractile proteins and metabolic muscle enzymes as revealed by label-free mass spectrometry +T2 - BIOSCIENCE REPORTS +LA - English +KW - amyotrophic lateral sclerosis +KW - motor neuron disease +KW - muscle proteomics +KW - muscular atrophy +KW - skeletal muscle proteome +KW - wobbler mouse +KW - AMYOTROPHIC-LATERAL-SCLEROSIS +KW - HUMAN SKELETAL-MUSCLE +KW - SPINAL-CORD +KW - WOBBLER MOUSE +KW - FIBER TYPES +KW - PROTEOMIC ASSESSMENT +KW - BIOMARKER DISCOVERY +KW - MUSCULAR-DYSTROPHY +KW - RAT GASTROCNEMIUS +KW - SOLEUS MUSCLES +AB - While the long-term physiological adaptation of the neuromuscular system to changed functional demands is usually reflected by unilateral skeletal muscle transitions, the progressive degeneration of distinct motor neuron populations is often associated with more complex changes in the abundance and/or isoform expression pattern of contractile proteins and metabolic enzymes. In order to evaluate these intricate effects of primary motor neuronopathy on the skeletal muscle proteome, label-free MS was employed to study global alterations in the WR (wobbler) mouse model of progressive neurodegeneration. In motor neuron disease, fibre-type specification and the metabolic weighting of bioenergetic pathways appear to be strongly influenced by both a differing degree of a subtype-specific vulnerability of neuromuscular synapses and compensatory mechanisms of fibre-type shifting. Proteomic profiling confirmed this pathobiochemical complexity of disease-induced changes and showed distinct alterations in 72 protein species, including a variety of fibre-type-specific isoforms of contractile proteins, metabolic enzymes, metabolite transporters and ion-regulatory proteins, as well as changes in molecular chaperones and various structural proteins. Increases in slow myosin light chains and the troponin complex and a decrease in fast MBP (myosin-binding protein) probably reflect the initial preferential loss of the fast type of neuromuscular synapses in motor neuron disease. +AD - Natl Univ Ireland, Dept Biol, Maynooth, Kildare, Ireland AD - Aarhus Univ, Dept Mol Biol & Genet, Aarhus, Denmark AD - Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland C3 - Maynooth University C3 - Aarhus University C3 - Dublin City University FU - BioAT programme of the Irish Higher Education Authority (HEA PRTLI cycle 5) +FX - This work was supported by the BioAT programme of the Irish Higher Education Authority (HEA PRTLI cycle 5). The Irish Higher Education Authority supported a laboratory visit of the Maynooth team in Denmark. +PU - PORTLAND PRESS LTD +PI - LONDON +PA - CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND +SN - 0144-8463 +SN - 1573-4935 +J9 - BIOSCIENCE REP +JI - Biosci. Rep. +PY - 2014 +VL - 34 +SP - 331 +EP - 343 +C7 - e00119 +DO - 10.1042/BSR20140029 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000341943100003 +N1 - Times Cited in Web of Science Core Collection: 8 +Total Times Cited: 9 +Cited Reference Count: 77 +ER - + +TY - JOUR +AU - von Leden, RE +AU - Cooney, SJ +AU - Ferrara, TM +AU - Zhao, YJ +AU - Dalgard, CL +AU - Anders, JJ +AU - Byrnes, KR +TI - 808nm Wavelength Light Induces a Dose-Dependent Alteration in Microglial Polarization and Resultant Microglial Induced Neurite Growth +T2 - LASERS IN SURGERY AND MEDICINE +LA - English +KW - alternative activation +KW - biostimulation +KW - classical activation +KW - light therapy +KW - low power laser irradiation +KW - low level laser therapy +KW - photobiomodulation +KW - M1 +KW - M2 +KW - SPINAL-CORD-INJURY +KW - POWER LASER IRRADIATION +KW - THERAPY +KW - LEVEL +KW - REGENERATION +KW - MACROPHAGES +KW - CELLS +KW - MODEL +KW - EXPRESSION +KW - SYSTEM +AB - Background and Objective Despite the success of using photobiomodulation (PBM), also known as low level light therapy, in promoting recovery after central nervous system (CNS) injury, the effect of PBM on microglia, the primary mediators of immune and inflammatory response in the CNS, remains unclear. Microglia exhibit a spectrum of responses to injury, with partial or full polarization into pro- and anti-inflammatory phenotypes. Pro-inflammatory (M1 or classically activated) microglia contribute to chronic inflammation and neuronal toxicity, while anti-inflammatory (M2 or alternatively activated) microglia play a role in wound healing and tissue repair; microglia can fall anywhere along this spectrum in response to stimulation. Materials and Methods The effect of PBM on microglial polarization therefore was investigated using colorimetric assays, immunocytochemistry, proteomic profiling and RT-PCR in vitro after exposure of primary microglia or BV2 microglial cell line to PBM of differing energy densities (0.2, 4, 10, and 30J/cm2, 808nm wavelength, 50mW output power). Results PBM has a dose-dependent effect on the spectrum of microglial M1 and M2 polarization. Specifically, PBM with energy densities between 4 and 30J/cm2 induced expression of M1 markers in microglia. Markers of the M2 phenotype, including CD206 and TIMP1, were observed at lower energy densities of 0.210J/cm2. In addition, co-culture of PBM or control-treated microglia with primary neuronal cultures demonstrated a dose-dependent effect of PBM on microglial-induced neuronal growth and neurite extension. Conclusion These data suggest that the ArndtSchulz law as applied to PBM for a specific bioassay does not hold true in cells with a spectrum of responses, and that PBM can alter microglial phenotype across this spectrum in a dose-dependent manner. These data are therefore of important relevance to not only therapies in the CNS but also to understanding of PBM effects and mechanisms. Lasers Surg. Med. (c) 2013 Wiley Periodicals, Inc. +AD - Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD USA C3 - Uniformed Services University of the Health Sciences - USA FU - American Society for Lasers in Surgery and Medicine Research +FX - Contract grant sponsor: American Society for Lasers in Surgery and Medicine Research +PU - WILEY +PI - HOBOKEN +PA - 111 RIVER ST, HOBOKEN 07030-5774, NJ USA +SN - 0196-8092 +SN - 1096-9101 +J9 - LASER SURG MED +JI - Lasers Surg. Med. +DA - APR +PY - 2013 +VL - 45 +IS - 4 +SP - 253 +EP - 263 +DO - 10.1002/lsm.22133 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000318306900008 +N1 - Times Cited in Web of Science Core Collection: 42 +Total Times Cited: 43 +Cited Reference Count: 34 +ER - + +TY - JOUR +AU - Abou-Abbass, H +AU - Bahmad, H +AU - Abou-El-Hassan, H +AU - Zhu, R +AU - Zhou, SY +AU - Dong, X +AU - Hamade, E +AU - Mallah, K +AU - Zebian, A +AU - Ramadan, N +AU - Mondello, S +AU - Fares, J +AU - Comair, Y +AU - Atweh, S +AU - Darwish, H +AU - Zibara, K +AU - Mechref, Y +AU - Kobeissy, F +TI - Deciphering glycomics and neuroproteomic alterations in experimental traumatic brain injury: Comparative analysis of aspirin and clopidogrel treatment +T2 - ELECTROPHORESIS +LA - English +KW - Aspirin +KW - Clopidogrel +KW - Neuroproteomics +KW - PTMs +KW - TBI +KW - MANNOSE-BINDING LECTIN +KW - MASS-SPECTROMETRIC ANALYSIS +KW - SOLID-PHASE PERMETHYLATION +KW - SPINAL-CORD-INJURY +KW - INTRACRANIAL HEMORRHAGE +KW - CEREBRAL-ISCHEMIA +KW - PROTEOMIC IDENTIFICATION +KW - PLATELET DYSFUNCTION +KW - ACETYLSALICYLIC-ACID +KW - AUTOMATED ANNOTATION +AB - As populations age, the number of patients sustaining traumatic brain injury (TBI) and concomitantly receiving preinjury antiplatelet therapy such as aspirin (ASA) and clopidogrel (CLOP) is rising. These drugs have been linked with unfavorable clinical outcomes following TBI, where the exact mechanism(s) involved are still unknown. In this novel work, we aimed to identify and compare the altered proteome profile imposed by ASA and CLOP when administered alone or in combination, prior to experimental TBI. Furthermore, we assessed differential glycosylation PTM patterns following experimental controlled cortical impact model of TBI, ASA, CLOP, and ASA + CLOP. Ipsilateral cortical brain tissues were harvested 48 h postinjury and were analyzed using an advanced neuroproteomics LC-MS/MS platform to assess proteomic and glycoproteins alterations. Of interest, differential proteins pertaining to each group (22 in TBI, 41 in TBI + ASA, 44 in TBI + CLOP, and 34 in TBI + ASA + CLOP) were revealed. Advanced bioinformatics/systems biology and clustering analyses were performed to evaluate biological networks and protein interaction maps illustrating molecular pathways involved in the experimental conditions. Results have indicated that proteins involved in neuroprotective cellular pathways were upregulated in the ASA and CLOP groups when given separately. However, ASA + CLOP administration revealed enrichment in biological pathways relevant to inflammation and proinjury mechanisms. Moreover, results showed differential upregulation of glycoproteins levels in the sialylated N-glycans PTMs that can be implicated in pathological changes. Omics data obtained have provided molecular insights of the underlying mechanisms that can be translated into clinical bedside settings. +AD - Amer Univ Beirut, Dept Biochem & Mol Genet, Fac Med, Beirut, Lebanon AD - Beirut Arab Univ, Fac Med, Beirut, Lebanon AD - Amer Univ Beirut, Dept Anat Cell Biol & Physiol Sci, Fac Med, Beirut, Lebanon AD - Amer Univ Beirut, Fac Med, Beirut, Lebanon AD - Texas Tech Univ, Dept Chem & Biochem, Lubbock, TX 79409 USA AD - Lebanese Univ, DSST, Lab Stem Cells ER045, Beirut, Lebanon AD - Lebanese Univ, Dept Biol, Fac Sci 1, Beirut, Lebanon AD - Univ Messina, Dept Neurosci, Messina, Italy AD - Lebanese Amer Univ, Div Neurosurg, Dept Surg, Beirut, Lebanon AD - Amer Univ Beirut, Dept Neurol, Fac Med, Beirut, Lebanon AD - Amer Univ Beirut, Fac Med, Sch Nursing, New York, NY USA C3 - American University of Beirut C3 - Beirut Arab University C3 - American University of Beirut C3 - American University of Beirut C3 - Texas Tech University System C3 - Texas Tech University C3 - Lebanese University C3 - Lebanese University C3 - University of Messina C3 - Lebanese American University C3 - American University of Beirut C3 - American University of Beirut C3 - American University of Beirut FU - National Council for Scientific Research (CNRS), Lebanon; NIH [5R01GM112490-02] +FX - This work was supported by the National Council for Scientific Research (CNRS), Lebanon, for the grant entitled "The Effect of Aspirin and Clopidogrel on Bleeding, platelet aggregation and Neuronal Damage after Moderate Brain Injury"; PI: Professor Samir Atweh, MD. This work was also partially supported by a grant from the NIH (5R01GM112490-02) for Professor Dr. Yehia Mechref. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. +PU - WILEY +PI - HOBOKEN +PA - 111 RIVER ST, HOBOKEN 07030-5774, NJ USA +SN - 0173-0835 +SN - 1522-2683 +J9 - ELECTROPHORESIS +JI - Electrophoresis +DA - JUN +PY - 2016 +VL - 37 +IS - 11 +SP - 1562 +EP - 1576 +DO - 10.1002/elps.201500583 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000379135200018 +N1 - Times Cited in Web of Science Core Collection: 25 +Total Times Cited: 26 +Cited Reference Count: 99 +ER - + +TY - JOUR +AU - Okazaki, S +AU - Hishimoto, A +AU - Otsuka, I +AU - Watanabe, Y +AU - Numata, S +AU - Boku, S +AU - Shimmyo, N +AU - Kinoshita, M +AU - Inoue, E +AU - Ohmori, T +AU - Someya, T +AU - Sora, I +TI - Increased serum levels and promoter polymorphisms of macrophage migration inhibitory factor in schizophrenia +T2 - PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY +LA - English +KW - Schizophrenia +KW - MIF +KW - Serum protein +KW - Postmortem brain +KW - Microsatellite +KW - SPINAL-CORD-INJURY +KW - JUVENILE IDIOPATHIC ARTHRITIS +KW - ELEVATED CIRCULATING LEVELS +KW - ACTIVATED PROTEIN-KINASE +KW - FACTOR MIF +KW - MOUSE MODEL +KW - RAT-BRAIN +KW - FUNCTIONAL POLYMORPHISMS +KW - RHEUMATOID-ARTHRITIS +KW - ASSOCIATION ANALYSIS +AB - Background: Numerous studies have suggested that an immune system imbalance plays an important role in schizophrenia. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine. It plays multiple roles in various biological processes, including inflammation and neurogenesis. Furthermore, several exhaustive serum proteomic profiling studies have identified MIF as a potential biomarker of schizophrenia. Here, we investigate MIF protein levels in serum and postmortem prefrontal cortex in patients with schizophrenia and controls. Moreover, we investigate the association of two functional polymorphisms in the MIF gene promoter region (MIF-794CATT(5-8) microsatellite and MIF-173G/C single-nucleotide polymorphism [SNP]) with schizophrenia. + Methods: We measured serum MIF levels with an enzyme-linked immunosorbent assay (ELISA) (51 patients vs. 86 controls) and postmortem brain MIF levels with a western blotting assay (18 patients vs. 22 controls). Subsequently, we genotyped the MIF-794CATT(5-8) microsatellite with a fluorescence-based fragment assay and the MIF-173G/C SNP with a TaqMan SNP genotyping assay (1483 patients vs. 1454 controls). + Results: Serum MIF levels were significantly higher in patients with schizophrenia than in controls (p = 0.00118), and were positively correlated with antipsychotic dose (Spearman's r = 0.222, p = 0.0402). In addition, an earlier age of onset was observed in patients with a high serum MIF level (>= 40 ng/mL) than those with a low serum MIF level (< 40 ng/mL) (p = 0.0392). However, postmortem brain MIF levels did not differ between patients with schizophrenia and controls. The association study revealed that the CATT(6)-G haplotype was nominally significantly associated with schizophrenia (p= 0.0338), and that the CATT(6) allele and CATT(6)-G haplotype were significantly associated with female adolescent-onset schizophrenia (AsOS) (corrected p = 0.0222 and p= 0.0147, respectively). + Conclusions: These results suggest that serum MIF level is a potential pharmacodynamic and/or monitoring marker of schizophrenia, and is related to a novel antipsychotic effect beyond dopamine antagonism. Furthermore, the MIF gene polymorphisms are associated with the risk for schizophrenia especially in adolescent females, and are potential stratification markers of schizophrenia. Further studies of MIF are warranted to elucidate the pathophysiology of schizophrenia and the effects of antipsychotics. +AD - Kobe Univ, Grad Sch Med, Dept Psychiat, Kobe, Hyogo, Japan AD - Niigata Univ, Grad Sch Med & Dent Sci, Dept Psychiat, Niigata, Japan AD - Tokushima Univ, Grad Sch Biomed Sci, Dept Psychiat, Tokushima, Japan C3 - Kobe University C3 - Niigata University C3 - Tokushima University FU - JSPS KAKENHI [JP26461718, JP15K19727]; Grants-in-Aid for Scientific Research [17K16371] Funding Source: KAKEN +FX - This work was supported in part by JSPS KAKENHI grant numbers JP26461718 and JP15K19727. We thank Yasuko Nagashima, Akiko Seo, and Makiko Ohnishi for providing technical assistance. +PU - PERGAMON-ELSEVIER SCIENCE LTD +PI - OXFORD +PA - THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND +SN - 0278-5846 +SN - 1878-4216 +J9 - PROG NEURO-PSYCHOPH +JI - Prog. Neuro-Psychopharmacol. Biol. Psychiatry +DA - APR 20 +PY - 2018 +VL - 83 +SP - 33 +EP - 41 +DO - 10.1016/j.pnpbp.2018.01.001 +WE - Science Citation Index Expanded (SCI-EXPANDED) WE - Social Science Citation Index (SSCI) AN - WOS:000424703700005 +N1 - Times Cited in Web of Science Core Collection: 19 +Total Times Cited: 21 +Cited Reference Count: 93 +ER - + +TY - JOUR +AU - Ge, LT +AU - Zhuo, Y +AU - Wu, P +AU - Liu, YS +AU - Qi, LY +AU - Teng, XH +AU - Duan, D +AU - Chen, P +AU - Lu, M +TI - Olfactory ensheathing cells facilitate neurite sprouting and outgrowth by secreting high levels of hevin +T2 - JOURNAL OF CHEMICAL NEUROANATOMY +LA - English +KW - Olfactory ensheathing cells +KW - Astrocytes +KW - Secretome +KW - Hevin +KW - Neurite sprouting +KW - EXTRACELLULAR-MATRIX GLYCOPROTEIN +KW - SPINAL-CORD +KW - FUNCTIONAL RECOVERY +KW - SHOTGUN PROTEOMICS +KW - PLASMA-MEMBRANE +KW - SCHWANN-CELLS +KW - UP-REGULATION +KW - STEM-CELLS +KW - SPARC +KW - TRANSPLANTATION +AB - Transplantation of olfactory ensheathing cells (OECs) has been shown to enhance synapse formation. However, the mechanisms underlying this effect are not completely understood. We performed profiling of the OEC and astrocyte secretomes via a proteomics approach, in case hevin secreted by astrocytes might be involved in the formation of synapses. Semi-quantitative proteomic analysis revealed that 25 proteins were highly expressed, and 22 were weakly expressed in OEC conditioned medium compared with astrocyte conditioned medium. These molecules are highly associated with neural differentiation and regeneration, enzyme regulatory activity, and growth factor binding. The quantification data of clusterin, fibronectin, hevin, insulin-like growth factor binding protein 2 and secreted protein acidic and rich in cysteine were further confirmed by western blotting. Moreover, the addition of hevin in the culture medium improved neurite sprouting and outgrowth of differentiated neural stem cells. The greater expression of hevin in OEC conditioned medium than in astrocyte conditioned medium was associated with a greater capacity of synaptic formation. Thus, our results indicate that soluble factors secreted by OECs provide a permissive environment for nerve repair, and hevin is one of the key molecules facilitating neurite sprouting and outgrowth. +AD - Hunan Normal Univ, Coll Life Sci, Natl & Local Joint Engn Lab Anim Peptide Drug Dev, Changsha, Peoples R China AD - Hunan Normal Univ, Hosp PLA 921, Affiliated Hosp 2, Hunan Prov Key Lab Neurorestoratol, Changsha, Peoples R China AD - Hunan Agr Univ, Hunan Key Lab Tradit Chinese Vet Med, Changsha, Peoples R China C3 - Hunan Normal University C3 - Hunan Normal University C3 - Hunan Agricultural University FU - National Natural Science Foundation of China [31670838, 31370817]; Scientific Research Fund of the Hunan Provincial Education Department [16B159]; Hunan Provincial Innovation Foundation for Postgraduates +FX - This work was supported by the National Natural Science Foundation of China (31670838, 31370817), the Scientific Research Fund of the Hunan Provincial Education Department (16B159), and the Hunan Provincial Innovation Foundation for Postgraduates (NO.CX2018B309, NO.CX2018B240). +PU - ELSEVIER +PI - AMSTERDAM +PA - RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS +SN - 0891-0618 +SN - 1873-6300 +J9 - J CHEM NEUROANAT +JI - J. Chem. Neuroanat. +DA - MAR +PY - 2020 +VL - 104 +C7 - 101728 +DO - 10.1016/j.jchemneu.2019.101728 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000519655700006 +N1 - Times Cited in Web of Science Core Collection: 5 +Total Times Cited: 5 +Cited Reference Count: 40 +ER - + +TY - JOUR +AU - Wu, JW +AU - Yan, JL +AU - Hua, Z +AU - Jia, JY +AU - Zhou, ZT +AU - Zhang, JF +AU - Li, J +AU - Zhang, J +TI - Identification of molecular signatures in acute myocardial infarction based on integrative analysis of proteomics and transcriptomics +T2 - GENOMICS +LA - English +KW - Acute myocardial infarction +KW - Proteomics +KW - Transcriptomics +KW - itgb2 +KW - Coro1a +KW - PROTEIN-INTERACTION NETWORKS +KW - ANALYSIS REVEALS +KW - TYROSINE KINASE +KW - GLOBAL BURDEN +KW - IMPROVES +KW - CORONIN +KW - DYSFUNCTION +KW - DIAGNOSIS +KW - PACKAGE +KW - DISEASE +AB - Background: Myocardial infarction (MI) is one of the most serious cardiovascular diseases, characterized by a rapid and irreversible decline in myocardial function. Early detection of patients with MI and prolonging the optimal therapeutic window of acute myocardial infarction (AMI) are particularly important. This study aimed to identify the diagnostic biomarkers and novel therapeutic targets for acute myocardial infarction.Method: We generated the AMI mouse models by ligating the proximal left anterior descending coronary artery. Six time points-Sham, AMI 10-min, 1-h, 6-h, 24-h, and 72-h-were chosen to examine the molecular changes that occur during the AMI process. RNA-seq and DIA-MS were performed on the infarcted left ventricular tissues of AMI mice at each time point. Co-expression pattern genes were screened from myocardial infarction samples at different time points by time-series analysis. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to examine these genes. Using the Interactive Gene/Protein Retrieval Tool (STRING) database, the protein-protein interaction network (PPI) was constructed and the hub genes were identified. In order to evaluate the diagnostic value of hub genes, a receiver operating characteristic (ROC) curve was constructed. An independent data set, GSE163772, confirmed the diagnostic value of hub genes further.Result: We obtained the expression profiles at different time points after the occurrence of heart failure through high-throughput sequencing, and found 167 genes with similar expression patterns through time series analysis. The immune response and immune-related pathways had the greatest enrichment of these genes. Among them, Itgb2 Syk, Tlr4, Tlr2, Itgax, and Lcp2 may play key roles as hub genes. Combined with the results of proteomic analysis, it was found that the expression of Coro1a in both omics increased with time. The results of external validation showed that TLR2, ITGAX, and LCP2 had good predictive ability for AMI diagnosis.Conclusion: Itgb2, Syk, Tlr4, Tlr2, Itgax, Lcp2 and Coro1a are considered to be the seven key genes significantly associated with AMI. Our results may provide potential targets for the prevention of adverse ventricular remodeling and the treatment of AMI. +AD - Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Med, Dept Gynecol, Shanghai, Peoples R China AD - Tongji Univ, Tongji Hosp, Orthopaed Dept,Sch Med, Key Lab Spine & Spinal Cord Injury Repair & Regene, Shanghai, Peoples R China AD - Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Cardiol, Shanghai, Peoples R China C3 - Tongji University C3 - Tongji University C3 - Tongji University FU - Outstanding Technology Leader Project of Shanghai 2023 Science and Technology Innovation Action Plan [23XD1433900]; Shangha Committee of Science and Technoloay. China Shanghai [227R1463700] +FX - This work was supported by Outstanding Technology Leader Project of Shanghai 2023 Science and Technology Innovation Action Plan (Grant No.23XD1433900) ; Shangha Committee of Science and Technoloay. China (Grant No 227R1463700) Shanghai. +PU - ACADEMIC PRESS INC ELSEVIER SCIENCE +PI - SAN DIEGO +PA - 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA +SN - 0888-7543 +SN - 1089-8646 +J9 - GENOMICS +JI - Genomics +DA - SEP +PY - 2023 +VL - 115 +IS - 5 +C7 - 110701 +DO - 10.1016/j.ygeno.2023.110701 +C6 - AUG 2023 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:001094533800001 +N1 - Times Cited in Web of Science Core Collection: 3 +Total Times Cited: 3 +Cited Reference Count: 70 +ER - + +TY - JOUR +AU - Idini, M +AU - Wieringa, P +AU - Rocchiccioli, S +AU - Nieddu, G +AU - Ucciferri, N +AU - Formato, M +AU - Lepedda, A +AU - Moroni, L +TI - Glycosaminoglycan functionalization of electrospun scaffolds enhances Schwann cell activity +T2 - ACTA BIOMATERIALIA +LA - English +KW - Electrospinning +KW - Schwann cells +KW - Neural regeneration +KW - Proteoglycans +KW - PERIPHERAL-NERVE REGENERATION +KW - CHONDROITIN SULFATE +KW - GROWTH-FACTOR +KW - SCIATIC-NERVE +KW - SPINAL-CORD +KW - IN-VITRO +KW - CONDUITS +KW - SYNDECAN-4 +KW - GRAFTS +KW - REPAIR +AB - Nerve fibers of the peripheral nervous system (PNS) have a remarkable ability to regenerate up to an almost complete recovery of normal function following a crush or a Sunderland Type II injury. This process is governed by glial cells, known as Schwann cells, through their unique capacity to dedifferentiate into cells that drive the healing process. Despite that many progresses have occurred in restorative medicine and microsurgery, the regenerative process after a severe lesion of a major nerve trunk (e.g., Sunderland Types III-V) is often incomplete and functional recovery is unsatisfactory. In this aspect, it is known that glycosaminoglycans (GAGs) of the extracellular matrix are involved in proliferation, synaptogenesis, neural plasticity, and regeneration of the PNS. Here, we developed poly(caprolactone) (PCL) fibrous scaffolds functionalized with GAGs, which allowed us to assess their influence on the adhesion, proliferation, and differentiation of Schwann cells. We found that both aligned and random fiber scaffolds functionalized with GAGs resulted in increased cell proliferation on day 1. In addition, aligned functionalized scaffolds also resulted in increased GAG presence on day 1, probably because of cell extracellular matrix (ECM) formation and an increased syndecan-4 expression on day 7. A different modification and activation of Schwann cells in the presence of GAG versus no-GAG scaffolds was underlined by proteomic comparative analysis, where a general downregulation of the expression of intracellular/structural and synthetic proteins was shown on day 7 for GAG-functionalized scaffolds with regard to the nonfunctionalized ones. In conclusion, we have shown that GAG-functionalized scaffolds are effective in modulating Schwann cell behavior in terms of adhesion, proliferation, and differentiation and should be considered in strategies to improve PNS repair. + Statement of Significance + Nerve fibers functional recovery following a severe trauma of the Peripheral Nervous System (PNS) still represents a huge challenge for neurosurgery nowadays. In this respect, tissue engineering is committed to develop new constructs able to guide Schwann cells by mimicking the natural extracellular matrix environment. To this purpose, we successfully fabricated polycaprolactone (PCL) scaffolds with two well-defined fiber deposition patterns, functionalized with glycosaminoglycans (GAGs) and assessed for their potential as support for Schwann cells adhesion, growth and differentiation, by both classical biochemistry and LC-MS-based proteomic profiling. By this way, we showed that PCL-GAGs scaffolds could represent a promising artificial substrate that closely mimics the recently established pattern of Schwann cells migration into the regenerating nerve and, therefore, it should be considered in strategies to improve PNS repair. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. +AD - Univ Sassari, Dipartimento Sci Biomed, Viale S Pietro 43-B, I-07100 Sassari, Italy AD - Maastricht Univ, MERLN Inst Technol Inspired Regenerat Med, Dept Complex Tissue Regenerat, Univ Singel 40, NL-6229 ER Maastricht, Netherlands AD - CNR, Inst Clin Physiol, Via Moruzzi 1, I-56124 Pisa, Italy C3 - University of Sassari C3 - Maastricht University C3 - Maastricht University Medical Centre (MUMC) C3 - Consiglio Nazionale delle Ricerche (CNR) C3 - Istituto di Fisiologia Clinica (IFC-CNR) FU - Regione Autonoma della Sardegna [C.U.P. J86C18000270002] +FX - AJ Lepedda thanks Regione Autonoma della Sardegna for its financial support (POR - FSE 2014-2020 - Asse Prioritario 3 "Istruzione e Formazione" - Obiettivo tematico: 10, Priority d'investi-mento: 10ii, Obiettivo specifico: 10.5, Azione dell'Accordo di Partenariato 10.5.12 - C.U.P. J86C18000270002). +PU - ELSEVIER SCI LTD +PI - OXFORD +PA - THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND +SN - 1742-7061 +SN - 1878-7568 +J9 - ACTA BIOMATER +JI - Acta Biomater. +DA - SEP 15 +PY - 2019 +VL - 96 +SP - 188 +EP - 202 +DO - 10.1016/j.actbio.2019.06.054 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000486132900014 +N1 - Times Cited in Web of Science Core Collection: 31 +Total Times Cited: 33 +Cited Reference Count: 85 +ER - + +TY - JOUR +AU - Karlsson, O +AU - Michno, W +AU - Ransome, Y +AU - Hanrieder, J +TI - MALDI imaging delineates hippocampal glycosphingolipid changes associated with neurotoxin induced proteopathy following neonatal BMAA exposure +T2 - BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS +LA - English +KW - Imaging mass spectrometry +KW - Beta-N-methylamino-L-alanine (BMAA) +KW - Environmental toxin +KW - Protein pathology +KW - Gliosis +KW - Glycosphingolipids +KW - METHYLAMINO-L-ALANINE +KW - AMYOTROPHIC-LATERAL-SCLEROSIS +KW - HUMAN SPINAL-CORD +KW - MASS-SPECTROMETRY +KW - DEVELOPMENTAL-CHANGES +KW - BRAIN GANGLIOSIDES +KW - MOTOR-NEURONS +KW - RAT-BRAIN +KW - GUAM +KW - LOCALIZATION +AB - The environmental toxin S-N-methylamino-L-alanine (BMAA) has been proposed to contribute to neurodegenerative diseases. We have previously shown that neonatal exposure to BMAA results in dose-dependent cognitive impairments, proteomic alterations and progressive neurodegeneration in the hippocampus of adult rats. A high BMAA dose (460 mg/kg) also induced intracellular fibril formation, increased protein ubiquitination and enrichment of proteins important for lipid transport and metabolism. The aim of this study was therefore to elucidate the role of neuronal lipids in BMAA-induced neurodegeneration. By using matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS), we characterized the spatial lipid profile in the hippocampus of six month-old rats that were treated neonatally (postnatal days 9-10) with 460 mg/kg BMAA. Multivariate statistical analysis revealed long-term changes in distinct ganglioside species (GM, GD, GT) in the dentate gyrus. These changes could be a consequence of direct effects on ganglioside biosynthesis through the b-series (GM3-GD3-GD2-GD1b-GT1b) and may be linked to astrogliosis. Complementary immunohistochemistry experiments towards GFAP and sloop further verified the role of increased astrocyte activity in BMAA-induced brain damage. This highlights the potential of imaging MS for probing chemical changes associated with neuropathological mechanisms in situ. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. (C) 2016 Elsevier B.V. All rights reserved. +AD - Karolinska Inst, Dept Clin Neurosci, Ctr Mol Med, S-17176 Stockholm, Sweden AD - Uppsala Univ, Dept Pharmaceut Biosci Toxicol & Drug Safety, Box 591, S-75124 Uppsala, Sweden AD - Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA AD - Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Molndal Hosp, House 5, S-43180 Molndal, Sweden AD - Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave, Boston, MA 02115 USA AD - Chalmers Univ Technol, Dept Chem & Chem Engn, Analyt Chem, Kemivagen 10, S-41296 Gothenburg, Sweden AD - UCL, UCL Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England C3 - Karolinska Institutet C3 - Uppsala University C3 - Harvard University C3 - Harvard T.H. Chan School of Public Health C3 - University of Gothenburg C3 - Harvard University C3 - Harvard T.H. Chan School of Public Health C3 - Chalmers University of Technology C3 - University of London C3 - University College London FU - Swedish research council VR [2014-6447]; FORMAS; Royal Society of Arts and Sciences in Gothenburg; Carl Tryggers Stiftelse; Alzheimerfonden; Demensfonden; Jeanssons Stiftelsen; Ahlen Stiftelsen; Stiftelsen Gamla Tjanarinnor; Stohnes Stiftelse; Stiftelsen Wilhelm and Martina Lundgrens Vetenskapsfond +FX - The Swedish research council VR (#2014-6447, JH), FORMAS (OK), the Royal Society of Arts and Sciences in Gothenburg (KVVS, JH), Carl Tryggers Stiftelse (OK), Alzheimerfonden (JH), Demensfonden (JH), Jeanssons Stiftelsen (JH), Ahlen Stiftelsen (JH), Stiftelsen Gamla Tjanarinnor (JH), Stohnes Stiftelse (JH) and Stiftelsen Wilhelm and Martina Lundgrens Vetenskapsfond (JH) are acknowledged for financial support. The authors declare no conflict of interest. +PU - ELSEVIER SCIENCE BV +PI - AMSTERDAM +PA - PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS +SN - 1570-9639 +SN - 0006-3002 +J9 - BBA-PROTEINS PROTEOM +JI - BBA-Proteins Proteomics +DA - JUL +PY - 2017 +VL - 1865 +IS - 7 +SP - 740 +EP - 746 +DO - 10.1016/j.bbapap.2016.12.004 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000404825500002 +N1 - Times Cited in Web of Science Core Collection: 9 +Total Times Cited: 9 +Cited Reference Count: 56 +ER - + +TY - JOUR +AU - Jassam, YN +AU - Izzy, S +AU - Whalen, M +AU - McGavern, DB +AU - El Khoury, J +TI - Neuroimmunology of Traumatic Brain Injury: Time for a ParadigmShift +T2 - NEURON +LA - English +KW - TUMOR-NECROSIS-FACTOR +KW - CONTROLLED CORTICAL IMPACT +KW - SPINAL-CORD-INJURY +KW - MEMBRANE ATTACK COMPLEX +KW - SHOCK-PROTEIN PROTECTS +KW - NEURONAL CELL-DEATH +KW - AUTOIMMUNE T-CELLS +KW - CEREBROSPINAL-FLUID +KW - GENE-EXPRESSION +KW - INFLAMMATORY RESPONSE +AB - Traumatic brain injury (TBI) is a leading cause ofmorbidity and disability, with a considerable socioeconomic burden. Heterogeneity of pathoanatomical subtypes and diversity in the pathogenesis and extent of injury contribute to differences in the course and outcome of TBI. Following the primary injury, extensive and lasting damage is sustained through a complex cascade of events referred to as "secondary injury.'' Neuroinflammation is proposed as an important manipulable aspect of secondary injury in animal and human studies. Because neuroinflammation can be detrimental or beneficial, before developing immunomodulatory therapies, it is necessary to better understand the timing and complexity of the immune responses that follow TBI. With a rapidly increasing body of literature, there is a need for a clear summary of TBI neuroimmunology. This review presents our current understanding of the immune response to TBI in a chronological and compartment-based manner, highlighting early changes in gene expression and initial signaling pathways that lead to activation of innate and adaptive immunity. Based on recent advances in our understanding of innate immune cell activation, we propose a new paradigm to study innate immune cells following TBI that moves away from the existing M1/M2 classification of activation states toward a stimulus- and disease-specific understanding of polarization state based on transcriptomic and proteomic profiling. +AD - NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA AD - Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA AD - Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA AD - Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA AD - Harvard Med Sch, Boston, MA 02115 USA C3 - National Institutes of Health (NIH) - USA C3 - NIH National Institute of Neurological Disorders & Stroke (NINDS) C3 - Harvard University C3 - Massachusetts General Hospital C3 - Harvard University C3 - Brigham & Women's Hospital C3 - Harvard University C3 - Massachusetts General Hospital C3 - Harvard University C3 - Harvard Medical School FU - NIH intramural program; NIA grant [RF1AG051506]; NINDS grant [1R21HD086385] +FX - We thank Alan Hoofring in the NIH Medical Arts Design Section for his help with the illustration shown in Figure 1 and Matthew Russo (NINDS) for providing the images shown in Figure 2. This work was supported by the NIH intramural program (D.B.M. and Y.J.), NIA grant RF1AG051506 (J.E.K.), and NINDS grant 1R21HD086385 (M.W.). +PU - CELL PRESS +PI - CAMBRIDGE +PA - 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA +SN - 0896-6273 +SN - 1097-4199 +J9 - NEURON +JI - Neuron +DA - SEP 13 +PY - 2017 +VL - 95 +IS - 6 +SP - 1246 +EP - 1265 +DO - 10.1016/j.neuron.2017.07.010 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000410564100008 +N1 - Times Cited in Web of Science Core Collection: 484 +Total Times Cited: 548 +Cited Reference Count: 247 +ER - + +TY - JOUR +AU - Barbosa, M +AU - Gomes, C +AU - Sequeira, C +AU - Gonçalves-Ribeiro, J +AU - Pina, CC +AU - Carvalho, LA +AU - Moreira, R +AU - Vaz, SH +AU - Vaz, AR +AU - Brites, D +TI - Recovery of Depleted miR-146a in ALS Cortical Astrocytes Reverts Cell Aberrancies and Prevents Paracrine Pathogenicity on Microglia and Motor Neurons +T2 - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY +LA - English +KW - amyotrophic lateral sclerosis +KW - astrocyte-microglia communication +KW - astrocyte-motor neuron crosstalk +KW - calcium signaling aberrancies +KW - glycoursodeoxycholic acid +KW - reactive astrocytes +KW - small extracellular vesicles +KW - vinyl sulfone +KW - AMYOTROPHIC-LATERAL-SCLEROSIS +KW - FIBRILLARY ACIDIC PROTEIN +KW - TRANSGENIC-MOUSE MODEL +KW - PREGNANCY ZONE PROTEIN +KW - REACTIVE ASTROCYTES +KW - SPINAL-CORD +KW - GLYCOURSODEOXYCHOLIC ACID +KW - CEREBROSPINAL-FLUID +KW - DISEASE +KW - ACTIVATION +AB - Reactive astrocytes in Amyotrophic Lateral Sclerosis (ALS) change their molecular expression pattern and release toxic factors that contribute to neurodegeneration and microglial activation. We and others identified a dysregulated inflammatory miRNA profile in ALS patients and in mice models suggesting that they represent potential targets for therapeutic intervention. Such cellular miRNAs are known to be released into the secretome and to be carried by small extracellular vesicles (sEVs), which may be harmful to recipient cells. Thus, ALS astrocyte secretome may disrupt cell homeostasis and impact on ALS pathogenesis. Previously, we identified a specific aberrant signature in the cortical brain of symptomatic SOD1-G93A (mSOD1) mice, as well as in astrocytes isolated from the same region of 7-day-old mSOD1 mice, with upregulated S100B/HMGB1/Cx43/vimentin and downregulated GFAP. The presence of downregulated miR-146a on both cases suggests that it can be a promising target for modulation in ALS. Here, we upregulated miR-146a with pre-miR-146a, and tested glycoursodeoxycholic acid (GUDCA) and dipeptidyl vinyl sulfone (VS) for their immunoregulatory properties. VS was more effective in restoring astrocytic miR-146a, GFAP, S100B, HMGB1, Cx43, and vimentin levels than GUDCA, which only recovered Cx43 and vimentin mRNA. The miR-146a inhibitor generated typical ALS aberrancies in wild type astrocytes that were abolished by VS. Similarly, pre-miR-146a transfection into the mSOD1 astrocytes abrogated aberrant markers and intracellular Ca2+ overload. Such treatment counteracted miR-146a depletion in sEVs and led to secretome-mediated miR-146a enhancement in NSC-34-motor neurons (MNs) and N9-microglia. Secretome from mSOD1 astrocytes increased early/late apoptosis and FGFR3 mRNA in MNs and microglia, but not when derived from pre-miR-146a or VS-treated cells. These last strategies prevented the impairment of axonal transport and synaptic dynamics by the pathological secretome, while also averted microglia activation through either secretome, or their isolated sEVs. Proteomic analysis of the target cells indicated that pre-miR-146a regulates mitochondria and inflammation via paracrine signaling. We demonstrate that replenishment of miR-146a in mSOD1 cortical astrocytes with pre-miR-146a or by VS abrogates their phenotypic aberrancies and paracrine deleterious consequences to MNs and microglia. These results propose miR-146a as a new causal and emerging therapeutic target for astrocyte pathogenic processes in ALS. +AD - Univ Lisbon, Inst Invest Medicamento iMed ULisboa, Fac Farm, Lisbon, Portugal AD - Univ Lisbon, Inst Med Mol Joao Lobo Antunes, Fac Med, Lisbon, Portugal AD - Univ Lisbon, Inst Farmacol & Neurociencias, Fac Med, Lisbon, Portugal AD - Univ Lisbon, Dept Ciencias Farmaceut & Medicamento, Fac Farm, Lisbon, Portugal C3 - Universidade de Lisboa C3 - Universidade de Lisboa C3 - Universidade de Lisboa C3 - Universidade de Lisboa FU - Research Grant of the Santa Casa Scientific Research Program on ALS; Santa Casa da Misericordia de Lisboa (SCML), Portugal [ELA-2015-002]; Fundacao para a Ciencia e a Tecnologia (FCT) [PTDC/MED-NEU/31395/2017, PTDC/MED-QUI/30021/2017, UIDB/04138/2020, UIDP/04138/2020]; Programa Operacional Regional de Lisboa [LISBOA-01-0145-FEDER-031395]; Programa Operacional Competitividade e Internacionalizacao [LISBOA-01-0145-FEDER-031395]; FCT [SFRH/BD/129586/2017, SFRH/BD/102718/2014, SFRH/BPD/76590/2011, PD/BD/150342/2019]; SCML; Fundação para a Ciência e a Tecnologia [PTDC/MED-QUI/30021/2017, SFRH/BD/102718/2014, SFRH/BD/129586/2017, PD/BD/150342/2019] Funding Source: FCT +FX - This work was supported by the Research Grant of the Santa Casa Scientific Research Program on ALS, by Santa Casa da Misericordia de Lisboa (SCML), Portugal, Project Ref. ELA-2015-002 (to DB). Fundacao para a Ciencia e a Tecnologia (FCT) also supported the project PTDC/MED-NEU/31395/2017 (to DB), PTDC/MED-QUI/30021/2017 (to RM) and iMed.ULisboa (UIDB/04138/2020 and UIDP/04138/2020), together with Programa Operacional Regional de Lisboa and the Programa Operacional Competitividade e Internacionalizacao (LISBOA-01-0145-FEDER-031395 to DB). Individual fellowships MB (SFRH/BD/129586/2017), CG (SFRH/BD/102718/2014), AV (SFRH/BPD/76590/2011), and JG-R PD/BD/150342/2019 were from FCT. CS was a research fellowship recipient from SCML. The funding organization had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. +PU - FRONTIERS MEDIA SA +PI - LAUSANNE +PA - AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND +SN - 2296-634X +J9 - FRONT CELL DEV BIOL +JI - Front. Cell. Dev. Biol. +DA - APR 23 +PY - 2021 +VL - 09 +C7 - 634355 +DO - 10.3389/fcell.2021.634355 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000648071500001 +N1 - Times Cited in Web of Science Core Collection: 29 +Total Times Cited: 31 +Cited Reference Count: 147 +ER - + +TY - JOUR +AU - Wei, ZJ +AU - Fan, BY +AU - Ding, H +AU - Liu, Y +AU - Tang, HS +AU - Pan, DY +AU - Shi, JX +AU - Zheng, PY +AU - Shi, HY +AU - Wu, H +AU - Li, A +AU - Feng, SQ +TI - Proteomics analysis of Schwann cell-derived exosomes: a novel therapeutic strategy for central nervous system injury +T2 - MOLECULAR AND CELLULAR BIOCHEMISTRY +LA - English +KW - Schwann cell +KW - Exosomes +KW - Central nervous system +KW - Proteomics +KW - SPINAL-CORD-INJURY +KW - AXONAL REGENERATION +KW - NEURITE OUTGROWTH +KW - TRANSPLANTATION +KW - CDC42 +KW - REGGIE-1/FLOTILLIN-2 +KW - SUPPRESSION +KW - FIBRONECTIN +KW - EXPRESSION +KW - SURVIVAL +AB - Exosomes are nanometer-sized vesicles involved in intercellular communication, and they are released by various cell types. To learn about exosomes produced by Schwann cells (SCs) and to explore their potential function in repairing the central nervous system (CNS), we isolated exosomes from supernatants of SCs by ultracentrifugation, characterized them by electron microscopy and immunoblotting and determined their protein profile using proteomic analysis. The results demonstrated that Schwann cell-derived exosomes (SCDEs) were, on average, 106.5nm in diameter, round, and had cup-like concavity and expressed exosome markers CD9 and Alix but not tumor susceptibility gene (TSG) 101. We identified a total of 433 proteins, among which 398 proteins overlapped with the ExoCarta database. According to their specific functions, we identified 12 proteins that are closely related to CNS repair and classified them by different potential mechanisms, such as axon regeneration and inflammation inhibition. Gene Oncology analysis indicated that SCDEs are mainly involved in signal transduction and cell communication. Biological pathway analysis showed that pathways are mostly involved in exosome biogenesis, formation, uptake and axon regeneration. Among the pathways, the neurotrophin, PI3K-Akt and cAMP signaling pathways played important roles in CNS repair. Our study isolated SCDEs, unveiled their contents, presented potential neurorestorative proteins and pathways and provided a rich proteomics data resource that will be valuable for future studies of the functions of individual proteins in neurodegenerative diseases. +AD - Tianjin Med Univ, Gen Hosp, Dept Orthoped, Tianjin 300052, Peoples R China AD - Tianjin Med Univ, Gen Hosp, Tianjin Lung Canc Inst, Tianjin Key Lab Lung Canc Metastasis & Tumor Micr, Tianjin 300052, Peoples R China AD - Henan Prov Peoples Hosp, Dept Orthoped, Zhengzhou 450000, Henan, Peoples R China C3 - Tianjin Medical University C3 - Tianjin Medical University C3 - Zhengzhou University FU - NSFC Program [81330042, 81620108018, 81672171, 81702147]; Ministry of Science and Technology, China [2014DFR31210]; Tianjin Science and Technology Committee, China [13RCGFSY19000, 14ZCZDSY00044] +FX - We thanked the support of the following funding: NSFC Program (81330042, 81620108018, 81672171, 81702147), Ministry of Science and Technology, China (2014DFR31210), Tianjin Science and Technology Committee, China (13RCGFSY19000, 14ZCZDSY00044). +PU - SPRINGER +PI - DORDRECHT +PA - VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS +SN - 0300-8177 +SN - 1573-4919 +J9 - MOL CELL BIOCHEM +JI - Mol. Cell. Biochem. +DA - JUL +PY - 2019 +VL - 457 +IS - 1-2 +SP - 51 +EP - 59 +DO - 10.1007/s11010-019-03511-0 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000470332500006 +N1 - Times Cited in Web of Science Core Collection: 49 +Total Times Cited: 51 +Cited Reference Count: 63 +ER - + +TY - JOUR +AU - Muñiz-Castrillo, S +AU - Hedou, JJ +AU - Ambati, A +AU - Jones, D +AU - Vogrig, A +AU - Pinto, AL +AU - Benaiteau, M +AU - de Broucker, T +AU - Fechtenbaum, L +AU - Labauge, P +AU - Murnane, M +AU - Nocon, C +AU - Taifas, I +AU - de Pémille, CV +AU - Psimaras, D +AU - Joubert, B +AU - Dubois, V +AU - Wucher, V +AU - Desestret, V +AU - Mignot, E +AU - Honnorat, J +TI - Distinctive clinical presentation and pathogenic specificities of anti-AK5 encephalitis +T2 - BRAIN +LA - English +KW - adenylate kinase 5 +KW - limbic encephalitis +KW - human leucocyte antigen +KW - proteomics +KW - PARANEOPLASTIC CEREBELLAR DEGENERATION +KW - INFLUENCES IMMUNOLOGICAL PARAMETERS +KW - ANTI-LGI1 ENCEPHALITIS +KW - LIMBIC ENCEPHALITIS +KW - CELL-DEATH +KW - AUTOIMMUNITY +KW - ANTIBODY +KW - DISEASES +KW - INNATE +KW - KINASE +AB - Limbic encephalitis with antibodies against adenylate kinase 5 (AK5) has been difficult to characterize because of its rarity. + In this study, we identified 10 new cases and reviewed 16 previously reported patients, investigating clinical features, IgG subclasses, human leucocyte antigen and CSF proteomic profiles. + Patients with anti-AK5 limbic encephalitis were mostly male (20/26, 76.9%) with a median age of 66 years (range 48-94). The predominant symptom was severe episodic amnesia in all patients, and this was frequently associated with depression (17/25, 68.0%). Weight loss, asthenia and anorexia were also highly characteristic, being present in 11/25 (44.0%) patients. Although epilepsy was always lacking at disease onset, seizures developed later in a subset of patients (4/25, 16.0%). All patients presented CSF abnormalities, such as pleocytosis (18/25, 72.0%), oligoclonal bands (18/25, 72.0%) and increased Tau (11/14, 78.6%). Temporal lobe hyperintensities were almost always present at disease onset (23/26, 88.5%), evolving nearly invariably towards severe atrophy in subsequent MRIs (17/19, 89.5%). This finding was in line with a poor response to immunotherapy, with only 5/25 (20.0%) patients responding. IgG1 was the predominant subclass, being the most frequently detected and the one with the highest titres in nine CSF-serum paired samples. A temporal biopsy from one of our new cases showed massive lymphocytic infiltrates dominated by both CD4+ and CT8 + T cells, intense granzyme B expression and abundant macrophages/microglia. Human leucocyte antigen (HLA) analysis in 11 patients showed a striking association with HLA-B*08:01 [7/11, 63.6%; odds ratio (OR) = 13.4, 95% confidence interval (CI): 3.8-47.4], C*07:01 (8/11, 72.7%; OR = 11.0, 95% CI: 2.9-42.5), DRB1*03:01 (8/11, 72.7%; OR = 14.4, 95% CI: 3.7-55.7), DQB1*02:01 (8/11, 72.7%; OR = 13.5, 95% CI: 3.5-52.0) and DQA1*05:01 (8/11, 72.7%; OR = 14.4, 95% CI: 3.7-55.7) alleles, which formed the extended haplotype B8-C7-DR3-DQ2 in 6/11 (54.5%) patients (OR = 16.5, 95% CI: 4.8-57.1). Finally, we compared the CSF proteomic profile of five anti-AK5 patients with that of 40 control subjects and 10 cases with other more common non-paraneoplastic limbic encephalitis (five with antibodies against leucine-rich glioma inactivated 1 and five against contactin-associated protein-like 2), as well as 10 cases with paraneoplastic neurological syndromes (five with antibodies against Yo and five against Ma2). These comparisons revealed 31 and seven significantly upregulated proteins in anti-AK5 limbic encephalitis, respectively mapping to apoptosis pathways and innate/adaptive immune responses. These findings suggest that the clinical manifestations of anti-AK5 limbic encephalitis result from a distinct T cell-mediated pathogenesis, with major cytotoxicity-induced apoptosis leading to a prompt and aggressive neuronal loss, likely explaining the poor prognosis and response to immunotherapy. +AD - Hosp Civils Lyon, French Reference Ctr Paraneoplast Neurol Syndrome, Hop Neurol, F-69677 Bron, France AD - Univ Lyon, Univ Claude Bernard Lyon 1, Inst NeuroMyoGene, SynatAc Team,INSERM U1217 CNRS UMR 5310, F-69372 Lyon, France AD - Stanford Univ, Ctr Narcolepsy, Palo Alto, CA 94304 USA AD - Albany Med Ctr Hosp, Pathol & Lab Med, Albany, NY 12208 USA AD - Neurol Dept, Hop Pierre Paul Riquet, F-31300 Toulouse, France AD - Ctr Hosp St Denis, Hop Pierre Delafontaine, Neurol Dept, F-93200 St Denis, France AD - Ctr Hosp Henri Mondor, Neurol Dept, F-94000 Paris, France AD - Ctr Hosp Univ Montpellier, Neurol Dept, F-34295 Montpellier, France AD - Albany Med Ctr Hosp, Neurol Dept, Albany, NY 12208 USA AD - Ctr Hosp Dax, Neurol Dept, F-40100 Dax, France AD - Hop Instruct Armees Percy, Neurol Dept, F-92140 Clamart, France AD - Grp Hosp Paris St Joseph, Neurol Dept, F-75014 Paris, France AD - Hop Univ La Pitie Salpetriere Charles Foix, AP HP, Neurol Dept 2 Mazarin, F-75013 Paris, France AD - Univ Paris 06, Univ Sorbonnes, Brain & Spinal Cord Inst, INSERM U1127 CNRS UMR 7255, F-75013 Paris, France AD - EFS Auvergne Rhone Alpes, HLA Lab, French Blood Serv, F-69150 Lyon, France C3 - CHU Lyon C3 - Universite Claude Bernard Lyon 1 C3 - Institut National de la Sante et de la Recherche Medicale (Inserm) C3 - Stanford University C3 - Albany Medical College C3 - CHU de Toulouse C3 - Assistance Publique Hopitaux Paris (APHP) C3 - Universite Paris-Est-Creteil-Val-de-Marne (UPEC) C3 - Hopital Universitaire Henri-Mondor - APHP C3 - Universite de Montpellier C3 - CHU de Montpellier C3 - Albany Medical College C3 - Universite Paris Cite C3 - Hopital Paris Saint-Joseph C3 - Assistance Publique Hopitaux Paris (APHP) C3 - Hopital Universitaire Charles-Foix - APHP C3 - Sorbonne Universite C3 - Hopital Universitaire Pitie-Salpetriere - APHP C3 - Sorbonne Universite C3 - Institut National de la Sante et de la Recherche Medicale (Inserm) FU - Fondation pour la recherche medicale [FRM-DQ20170336751]; Agence Nationale de la Recherche (ANR), second Investissements d'Avenir program [ANR-18-RHUS-0012, ANR-11-LABX-0042]; Fundacion Alfonso Martin Escudero (Spain); National Institutes of Health [NIH-1U01NS120885] +FX - This study is supported by Fondation pour la recherche medicale (FRM-DQ20170336751). This work has been developed within the BETPSY project, which is supported by a public grant overseen by the Agence Nationale de la Recherche (ANR) as part of the second Investissements d'Avenir program (ANR-18-RHUS-0012), and has been performed within the framework of the LABEX CORTEX (ANR-11-LABX-0042) of Universite ' de Lyon operated by the ANR. S.M.-C. is supported by a research grant from Fundacio ' n Alfonso Marti ' n Escudero (Spain). E.M. and A.A. were supported by National Institutes of Health (NIH-1U01NS120885). +PU - OXFORD UNIV PRESS +PI - OXFORD +PA - GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND +SN - 0006-8950 +SN - 1460-2156 +J9 - BRAIN +JI - Brain +DA - SEP +PY - 2021 +VL - 144 +SP - 2709 +EP - 2721 +DO - 10.1093/brain/awab153 +C6 - APR 2021 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000733722200031 +N1 - Times Cited in Web of Science Core Collection: 24 +Total Times Cited: 26 +Cited Reference Count: 54 +ER - + +TY - JOUR +AU - Dauth, S +AU - Maoz, BM +AU - Sheehy, SP +AU - Hemphill, MA +AU - Murty, T +AU - Macedonia, MK +AU - Greer, AM +AU - Budnik, B +AU - Parker, KK +TI - Neural Circuits Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip +T2 - JOURNAL OF NEUROPHYSIOLOGY +LA - English +KW - brain-on-a-chip +KW - different brain regions +KW - protein expression +KW - electrophysiology +KW - metabolism +KW - HIPPOCAMPAL-NEURONS +KW - PROTEOMIC ANALYSIS +KW - CORTICAL-NEURONS +KW - SNARE COMPLEX +KW - SPINAL-CORD +KW - RAT MODELS +KW - CELL-TYPES +KW - NETWORKS +KW - INJURY +KW - SCHIZOPHRENIA +AB - Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. + NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the connection and communication of several brain regions, underlining the importance of developing multiregional brain in vitro models. We introduced a novel brain-on-a-chip model, implementing essential in vivo features, such as different brain areas and their functional connections. +AD - Harvard Univ, John A Paulson Sch Engn & Appl Sci, Wyss Inst Biol Inspired Engn, Dis Biophys Grp, 29 Oxford St,Rm 321, Cambridge, MA 02138 USA AD - Harvard Univ, Mass Spectrometry & Prote Resource Lab, Cambridge, MA 02138 USA C3 - Harvard University C3 - Harvard University FU - Wyss Institute for Biologically Inspired Engineering at Harvard University (John A. Paulson School of Engineering and Applied Sciences); Defense Advanced Research Projects Agency [W911NF-12-2-0036]; Congressionally Directed Medical Research Program through the United States Army [W81XWH-11-2-0057]; Emerald Grant entitled "Molecular Mechanisms of Diffuse Axonal Injury; National Science Foundation under NSF award [ECS-0335765]; Neural Imaging Center,National Institute of Neurological Disorders and Stroke P30 Core Center Grant [NS-072030] +FX - This research was sponsored by the Wyss Institute for Biologically Inspired Engineering at Harvard University (John A. Paulson School of Engineering and Applied Sciences) and the Defense Advanced Research Projects Agency under Cooperative Agreement no. W911NF-12-2-0036. This work was also supported by a Congressionally Directed Medical Research Program through the United States Army (no. W81XWH-11-2-0057) and an Emerald Grant entitled "Molecular Mechanisms of Diffuse Axonal Injury." This work was performed in part at the Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Infrastructure Network, which is supported by the National Science Foundation under NSF award no. ECS-0335765. CNS is part of Harvard University. The Neurobiology Imaging Facility is supported in part by the Neural Imaging Center as part of National Institute of Neurological Disorders and Stroke P30 Core Center Grant NS-072030. +PU - AMER PHYSIOLOGICAL SOC +PI - BETHESDA +PA - 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA +SN - 0022-3077 +SN - 1522-1598 +J9 - J NEUROPHYSIOL +JI - J. Neurophysiol. +DA - MAR 1 +PY - 2017 +VL - 117 +IS - 3 +SP - 1320 +EP - 1341 +DO - 10.1152/jn.00575.2016 +WE - Science Citation Index Expanded (SCI-EXPANDED) AN - WOS:000398162500038 +N1 - Times Cited in Web of Science Core Collection: 75 +Total Times Cited: 80 +Cited Reference Count: 68 +ER - + diff --git a/vignettes/.gitignore b/vignettes/.gitignore new file mode 100644 index 0000000..097b241 --- /dev/null +++ b/vignettes/.gitignore @@ -0,0 +1,2 @@ +*.html +*.R diff --git a/vignettes/basic_workflow.Rmd b/vignettes/basic_workflow.Rmd new file mode 100644 index 0000000..4b71c1e --- /dev/null +++ b/vignettes/basic_workflow.Rmd @@ -0,0 +1,45 @@ +--- +title: "basic_workflow" +output: rmarkdown::html_vignette +vignette: > + %\VignetteIndexEntry{basic_workflow} + %\VignetteEngine{knitr::rmarkdown} + %\VignetteEncoding{UTF-8} +--- + +```{r, include = FALSE} +knitr::opts_chunk$set( + collapse = TRUE, + comment = "#>" +) +``` + +```{r setup, message=FALSE, warning=FALSE} +library(retractionfindr) +library(tidyverse) +``` + + +Once you have your search (from Web of Science, PubMed, etc.), you can use `retractionfindr` functions to search for retractions. Export your search as a `.ris` file and use the `read_refs` function to read the file. Then use the `check_retracted` function to search for retractions. + +This returns a list of the number of retractions and the total number of records in the file, as well as a dataframe with all the references and a column indicating whether the reference is retracted or not. + +```{r load the data} +# First you need to upload a RIS file +# We use the read_refs function from synthesisr to read the RIS file +refs<-synthesisr::read_refs(system.file("extdata", "example.ris", package = "retractionfindr")) + +out<-check_retracted(refs) + +out$n_total +out$n_retracted + +``` + +You may wish to separate the retracted and non-retracted articles. You can do this using the `separate_retracted` function. + +```{r separate the retracted articles} +sep_refs<-separate_retracted(out$refs) +sep_refs[1] # retracted +#sep_refs[2] # non-retracted +``` \ No newline at end of file