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• W2994875504 endingPage "2100" @default.
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• W2994875504 abstract "<ns4:p>Emerging data point to important contributions of both autoimmune inflammation and progressive degeneration in the pathophysiology of multiple sclerosis (MS). Unfortunately, after decades of intensive investigation, the fundamental cause remains unknown. A large body of research on the immunobiology of MS has resulted in a variety of anti-inflammatory therapies that are highly effective at reducing brain inflammation and clinical/radiological relapses. However, despite potent suppression of inflammation, benefit in the more important and disabling progressive phase is extremely limited; thus, progressive MS has emerged as the greatest challenge for the MS research and clinical communities. Data obtained over the years point to a complex interplay between environment (e.g., the near-absolute requirement of Epstein–Barr virus exposure), immunogenetics (strong associations with a large number of immune genes), and an ever more convincing role of an underlying degenerative process resulting in demyelination (in both white and grey matter regions), axonal and neuro-synaptic injury, and a persistent innate inflammatory response with a seemingly diminishing role of T cell–mediated autoimmunity as the disease progresses. Together, these observations point toward a primary degenerative process, one whose cause remains unknown but one that entrains a nearly ubiquitous secondary autoimmune response, as a likely sequence of events underpinning this disease. Here, we briefly review what is known about the potential pathophysiological mechanisms, focus on progressive MS, and discuss the two main hypotheses of MS pathogenesis that are the topic of vigorous debate in the field: whether primary autoimmunity or degeneration lies at the foundation. Unravelling this controversy will be critically important for developing effective new therapies for the most disabling later phases of this disease.</ns4:p>" @default.
• W2994875504 created "2019-12-26" @default.
• W2994875504 creator A5028489612 @default.
• W2994875504 creator A5054101427 @default.
• W2994875504 date "2019-12-13" @default.
• W2994875504 modified "2023-10-13" @default.
• W2994875504 title "Recent advances in understanding multiple sclerosis" @default.
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• W2994875504 doi "https://doi.org/10.12688/f1000research.20906.1" @default.
• W2994875504 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6915812" @default.
• W2994875504 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31885862" @default.
• W2994875504 hasPublicationYear "2019" @default.

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