{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:00:15Z","timestamp":1789761615917,"version":"4.0.1"},"reference-count":54,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurobiology of Disease"],"published-print":{"date-parts":[[2024,3]]},"DOI":"10.1016\/j.nbd.2024.106414","type":"journal-article","created":{"date-parts":[[2024,1,21]],"date-time":"2024-01-21T02:59:19Z","timestamp":1705805959000},"page":"106414","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["PAD2 dysregulation and aberrant protein citrullination feature prominently in reactive astrogliosis and myelin protein aggregation in sporadic ALS"],"prefix":"10.1016","volume":"192","author":[{"given":"Issa O.","family":"Yusuf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Parsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyle W.","family":"Ostrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuoshang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.nbd.2024.106414_bb0005","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.jaut.2012.03.004","article-title":"Neuronal PAD4 expression and protein citrullination: possible role in production of autoantibodies associated with neurodegenerative disease","volume":"38","author":"Acharya","year":"2012","journal-title":"J. Autoimmun."},{"key":"10.1016\/j.nbd.2024.106414_bb0010","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/s41576-023-00592-y","article-title":"Amyotrophic lateral sclerosis: translating genetic discoveries into therapies","volume":"24","author":"Akcimen","year":"2023","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.nbd.2024.106414_bb0015","doi-asserted-by":"crossref","DOI":"10.1093\/brain\/awad232","article-title":"A data-driven study of Alzheimer\u2019s disease related amyloid and tau pathology progression","author":"Aksman","year":"2023","journal-title":"Brain."},{"key":"10.1016\/j.nbd.2024.106414_bb0020","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1006\/cbir.1993.1094","article-title":"Combined biochemical and immunocytochemical analyses of postmortem protein deimination in the rat spinal cord","volume":"17","author":"Asaga","year":"1993","journal-title":"Cell Biol. Int."},{"key":"10.1016\/j.nbd.2024.106414_bb0025","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","article-title":"A guided tour into subcellular colocalization analysis in light microscopy","volume":"224","author":"Bolte","year":"2006","journal-title":"J. Microsc."},{"key":"10.1016\/j.nbd.2024.106414_bb0030","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0197-4580(95)00021-6","article-title":"Staging of Alzheimer\u2019s disease-related neurofibrillary changes","volume":"16","author":"Braak","year":"1995","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.nbd.2024.106414_bb0035","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson\u2019s disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.nbd.2024.106414_bb0040","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jneuroim.2014.05.007","article-title":"Localisation of citrullinated proteins in normal appearing white matter and lesions in the central nervous system in multiple sclerosis","volume":"273","author":"Bradford","year":"2014","journal-title":"J. Neuroimmunol."},{"key":"10.1016\/j.nbd.2024.106414_bb0045","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/ana.23937","article-title":"Stages of pTDP-43 pathology in amyotrophic lateral sclerosis","volume":"74","author":"Brettschneider","year":"2013","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.nbd.2024.106414_bb0050","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1146\/annurev-biochem-061516-045115","article-title":"Protein Misfolding, amyloid formation, and human disease: a summary of Progress over the last decade","volume":"86","author":"Chiti","year":"2017","journal-title":"Annu. Rev. Biochem."},{"key":"10.1016\/j.nbd.2024.106414_bb0055","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s00018-022-04126-3","article-title":"Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives","volume":"79","author":"Ciesielski","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.nbd.2024.106414_bb0060","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1002\/art.21220","article-title":"Synovial intracellular citrullinated proteins colocalizing with peptidyl arginine deiminase as pathophysiologically relevant antigenic determinants of rheumatoid arthritis-specific humoral autoimmunity","volume":"52","author":"De Rycke","year":"2005","journal-title":"Arthritis Rheum."},{"key":"10.1016\/j.nbd.2024.106414_bb0065","first-page":"C723","article-title":"A practical guide to evaluating colocalization in biological microscopy","volume":"300","author":"Dunn","year":"2011","journal-title":"Am. J. Phys. Cell Phys."},{"key":"10.1016\/j.nbd.2024.106414_bb0070","doi-asserted-by":"crossref","first-page":"5413","DOI":"10.1021\/acs.chemrev.5b00003","article-title":"Chemical biology of protein arginine modifications in epigenetic regulation","volume":"115","author":"Fuhrmann","year":"2015","journal-title":"Chem. Rev."},{"key":"10.1016\/j.nbd.2024.106414_bb0075","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/oxfordjournals.jbchem.a133189","article-title":"Properties of peptidylarginine deiminase from the epidermis of newborn rats","volume":"89","author":"Fujisaki","year":"1981","journal-title":"J. Biochem."},{"key":"10.1016\/j.nbd.2024.106414_bb0080","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.77019","article-title":"Conservation and divergence of myelin proteome and oligodendrocyte transcriptome profiles between humans and mice","volume":"11","author":"Gargareta","year":"2022","journal-title":"Elife."},{"key":"10.1016\/j.nbd.2024.106414_bb0085","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.micron.2004.04.005","article-title":"Myelin basic protein-diverse conformational states of an intrinsically unstructured protein and its roles in myelin assembly and multiple sclerosis","volume":"35","author":"Harauz","year":"2004","journal-title":"Micron."},{"key":"10.1016\/j.nbd.2024.106414_bb0090","series-title":"The Inflammatory Puzzle: Piecing Together the Links between Neuroinflammation and Amyotrophic Lateral Sclerosis","author":"He","year":"2023"},{"key":"10.1016\/j.nbd.2024.106414_bb0095","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/nrneurol.2015.225","article-title":"Tau and neurodegenerative disease: the story so far","volume":"12","author":"Iqbal","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.nbd.2024.106414_bb0100","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/jnr.20431","article-title":"Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer\u2019s disease","volume":"80","author":"Ishigami","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.nbd.2024.106414_bb0105","doi-asserted-by":"crossref","first-page":"239","DOI":"10.3389\/fncel.2020.00239","article-title":"The CNS myelin proteome: deep profile and persistence after post-mortem delay","volume":"14","author":"Jahn","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.nbd.2024.106414_bb0110","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.2353\/ajpath.2008.080388","article-title":"Accumulation of citrullinated proteins by up-regulated peptidylarginine deiminase 2 in brains of scrapie-infected mice: a possible role in pathogenesis","volume":"173","author":"Jang","year":"2008","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.nbd.2024.106414_bb0115","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s00401-009-0625-x","article-title":"Involvement of peptidylarginine deiminase-mediated post-translational citrullination in pathogenesis of sporadic Creutzfeldt-Jakob disease","volume":"119","author":"Jang","year":"2010","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.nbd.2024.106414_bb0120","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s00401-016-1537-1","article-title":"Updated TDP-43 in Alzheimer\u2019s disease staging scheme","volume":"131","author":"Josephs","year":"2016","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.nbd.2024.106414_bb0125","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13024-021-00501-z","article-title":"Neuropathology and molecular diagnosis of Synucleinopathies","volume":"16","author":"Koga","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.nbd.2024.106414_bb0130","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ydbio.2011.04.015","article-title":"Protein deiminases: new players in the developmentally regulated loss of neural regenerative ability","volume":"355","author":"Lange","year":"2011","journal-title":"Dev. Biol."},{"key":"10.1016\/j.nbd.2024.106414_bb0135","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/jnc.12744","article-title":"Peptidylarginine deiminases: novel drug targets for prevention of neuronal damage following hypoxic ischemic insult (HI) in neonates","volume":"130","author":"Lange","year":"2014","journal-title":"J. Neurochem."},{"key":"10.1016\/j.nbd.2024.106414_bb0140","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3389\/fneur.2015.00204","article-title":"Protein Citrullination: a proposed mechanism for pathology in traumatic brain injury","volume":"6","author":"Lazarus","year":"2015","journal-title":"Front. Neurol."},{"key":"10.1016\/j.nbd.2024.106414_bb0145","doi-asserted-by":"crossref","first-page":"11387","DOI":"10.1523\/JNEUROSCI.3349-06.2006","article-title":"Increased citrullination of histone H3 in multiple sclerosis brain and animal models of demyelination: a role for tumor necrosis factor-induced peptidylarginine deiminase 4 translocation","volume":"26","author":"Mastronardi","year":"2006","journal-title":"J. Neurosci."},{"key":"10.1016\/j.nbd.2024.106414_bb0150","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41573-022-00612-2","article-title":"Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation","volume":"22","author":"Mead","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.nbd.2024.106414_bb0155","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1021\/acs.accounts.9b00024","article-title":"Protein arginine deiminases (PADs): biochemistry and chemical biology of protein Citrullination","volume":"52","author":"Mondal","year":"2019","journal-title":"Acc. Chem. Res."},{"key":"10.1016\/j.nbd.2024.106414_bb0160","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1046\/j.1471-4159.2002.00834.x","article-title":"Peptidylarginine deiminase: a candidate factor in demyelinating disease","volume":"81","author":"Moscarello","year":"2002","journal-title":"J. Neurochem."},{"key":"10.1016\/j.nbd.2024.106414_bb0165","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s11064-006-9144-5","article-title":"The role of citrullinated proteins suggests a novel mechanism in the pathogenesis of multiple sclerosis","volume":"32","author":"Moscarello","year":"2007","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.nbd.2024.106414_bb0170","first-page":"467","article-title":"Inhibition of peptidyl-arginine deiminases reverses protein-hypercitrullination and disease in mouse models of multiple sclerosis","volume":"6","author":"Moscarello","year":"2013","journal-title":"Dis. Model. Mech."},{"key":"10.1016\/j.nbd.2024.106414_bb0175","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1242\/dmm.000729","article-title":"Peptidylarginine deiminase 2 (PAD2) overexpression in transgenic mice leads to myelin loss in the central nervous system","volume":"1","author":"Musse","year":"2008","journal-title":"Dis. Model. Mech."},{"key":"10.1016\/j.nbd.2024.106414_bb0180","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1093\/brain\/awz099","article-title":"Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report","volume":"142","author":"Nelson","year":"2019","journal-title":"Brain."},{"key":"10.1016\/j.nbd.2024.106414_bb0185","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.neulet.2011.03.028","article-title":"Dual immunofluorescence study of citrullinated proteins in Parkinson diseased substantia nigra","volume":"495","author":"Nicholas","year":"2011","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.nbd.2024.106414_bb0190","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.neulet.2013.04.028","article-title":"Dual immunofluorescence study of citrullinated proteins in Alzheimer diseased frontal cortex","volume":"545","author":"Nicholas","year":"2013","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.nbd.2024.106414_bb0195","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s10787-023-01149-5","article-title":"Selective inhibition of peptidyl-arginine deiminase (PAD): can it control multiple inflammatory disorders as a promising therapeutic strategy?","volume":"31","author":"Padhy","year":"2023","journal-title":"Inflammopharmacology."},{"key":"10.1016\/j.nbd.2024.106414_bb0200","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/cne.21055","article-title":"Experimental autoimmune encephalomyelitis induction in peptidylarginine deiminase 2 knockout mice","volume":"498","author":"Raijmakers","year":"2006","journal-title":"J. Comp. Neurol."},{"key":"10.1016\/j.nbd.2024.106414_bb0205","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1126\/science.aag2590","article-title":"How neuroinflammation contributes to neurodegeneration","volume":"353","author":"Ransohoff","year":"2016","journal-title":"Science."},{"key":"10.1016\/j.nbd.2024.106414_bb0210","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.humimm.2021.01.017","article-title":"The role of immune-mediated alterations and disorders in ALS disease","volume":"82","author":"Rodrigues Lima-Junior","year":"2021","journal-title":"Hum. Immunol."},{"key":"10.1016\/j.nbd.2024.106414_bb0215","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41586-023-06437-2","article-title":"Molecular pathology of neurodegenerative diseases by cryo-EM of amyloids","volume":"621","author":"Scheres","year":"2023","journal-title":"Nature."},{"key":"10.1016\/j.nbd.2024.106414_bb0220","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1002\/jnr.22255","article-title":"Developmental and age-related changes of peptidylarginine deiminase 2 in the mouse brain","volume":"88","author":"Shimada","year":"2010","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.nbd.2024.106414_bb0225","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3389\/fonc.2019.00015","article-title":"Progression on Citrullination of proteins in gastrointestinal cancers","volume":"9","author":"Song","year":"2019","journal-title":"Front. Oncol."},{"key":"10.1016\/j.nbd.2024.106414_bb0230","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1038\/s41593-018-0235-9","article-title":"Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases","volume":"21","author":"Soto","year":"2018","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.nbd.2024.106414_bb0235","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.sbi.2019.01.024","article-title":"Peptidyl arginine deiminases: detection and functional analysis of protein citrullination","volume":"59","author":"Tilvawala","year":"2019","journal-title":"Curr. Opin. Struct. Biol."},{"issue":"691\u2013704","key":"10.1016\/j.nbd.2024.106414_bb0240","article-title":"The rheumatoid arthritis-associated Citrullinome","volume":"25","author":"Tilvawala","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"10.1016\/j.nbd.2024.106414_bb0245","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24043380","article-title":"Aggregation of disordered proteins associated with neurodegeneration","volume":"24","author":"Tsoi","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.nbd.2024.106414_bb0250","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2022.12.032","article-title":"Hallmarks of neurodegenerative diseases","volume":"186","author":"Wilson","year":"2023","journal-title":"Cell."},{"key":"10.1016\/j.nbd.2024.106414_bb0255","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1007\/s11064-016-1920-2","article-title":"Myelin basic protein Citrullination in multiple sclerosis: a potential therapeutic target for the pathology","volume":"41","author":"Yang","year":"2016","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.nbd.2024.106414_bb0260","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1093\/brain\/awad145","article-title":"Data-driven neuropathological staging and subtyping of TDP-43 proteinopathies","volume":"146","author":"Young","year":"2023","journal-title":"Brain."},{"key":"10.1016\/j.nbd.2024.106414_bb0265","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/B978-0-323-98817-9.00031-4","article-title":"Amyotrophic lateral sclerosis","volume":"196","author":"Younger","year":"2023","journal-title":"Handb. Clin. Neurol."},{"key":"10.1016\/j.nbd.2024.106414_bb0270","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s40478-022-01433-5","article-title":"Protein citrullination marks myelin protein aggregation and disease progression in mouse ALS models","volume":"10","author":"Yusuf","year":"2022","journal-title":"Acta Neuropathol. Commun."}],"container-title":["Neurobiology of Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996124000135?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996124000135?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T05:39:40Z","timestamp":1760852380000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0969996124000135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":54,"alternative-id":["S0969996124000135"],"URL":"https:\/\/doi.org\/10.1016\/j.nbd.2024.106414","relation":{},"ISSN":["0969-9961"],"issn-type":[{"value":"0969-9961","type":"print"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"PAD2 dysregulation and aberrant protein citrullination feature prominently in reactive astrogliosis and myelin protein aggregation in sporadic ALS","name":"articletitle","label":"Article Title"},{"value":"Neurobiology of Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.nbd.2024.106414","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"106414"}}