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Its role in the pathogenesis of MS is supported by histopathological analyses, genetic data, and numerous animal models of MS. All approved disease-modifying therapies that reduce clinical relapses and diminish the accumulation of lesions on neuroimaging are anti-inflammatory. Axonal loss and accelerated brain volume loss can also be detected from clinical disease onset throughout all stages. The expression of neurofilament light chain in cerebrospinal fluid and serum, a scaffolding protein in axons and dendrites, is a biomarker of neuronal injury associated with clinical relapses and reflects neuronal loss during episodes of acute inflammation. The recent association of human endogenous retrovirus (HERV) and its envelope proteins with MS illustrates a pathogenic pathway that causally links central nervous system (CNS)\u2013intrinsic proinflammatory effects and inhibition of myelin repair and neuroregeneration. A review of current data on the causal relationship between inflammation and neurodegeneration in MS identified numerous plausible pathomechanisms that link the two events. Observations from most experimental models appear to favor a pathogenesis in which inflammation precedes neurodegeneration.<\/jats:p>","DOI":"10.1177\/1352458519886943","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T11:10:37Z","timestamp":1572865837000},"page":"876-886","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":60,"title":["The temporal and causal relationship between inflammation and neurodegeneration in multiple sclerosis"],"prefix":"10.1177","volume":"26","author":[{"given":"Ron","family":"Milo","sequence":"first","affiliation":[{"name":"Department of Neurology, Barzilai Medical Center, Ashkelon, Israel\/Faculty of Health Sciences, Ben-Gurion University of the Negev, Be\u2019er Sheva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amos D","family":"Korczyn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navid","family":"Manouchehri","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"St\u00fcve","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas, TX, USA\/Neurology Section, Medical Service, VA North Texas Health Care System, Dallas, TX, USA\/Department of Neurology, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,11,4]]},"reference":[{"key":"bibr1-1352458519886943","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.10.040192.001101"},{"key":"bibr2-1352458519886943","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-013-1044-7"},{"key":"bibr3-1352458519886943","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000560"},{"key":"bibr4-1352458519886943","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000102"},{"key":"bibr5-1352458519886943","first-page":"554","volume":"141","author":"Charcot JM","year":"1868","journal-title":"Gaz Hop"},{"key":"bibr6-1352458519886943","doi-asserted-by":"crossref","unstructured":"Compston A, McDonald I, Noseworthy J, et al. 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