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An “outside-in” and “inside-out” consideration of complement in the multiple sclerosis brain: lessons from development and neurodegenerative diseases

Morgan, B. Paul ORCID:, Gommerman, Jennifer L. and Ramaglia, Valeria 2021. An “outside-in” and “inside-out” consideration of complement in the multiple sclerosis brain: lessons from development and neurodegenerative diseases. Frontiers in Cellular Neuroscience 14 , 600656. 10.3389/fncel.2020.600656

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The last 15 years have seen an explosion of new findings on the role of complement, a major arm of the immune system, in the central nervous system (CNS) compartment including contributions to cell migration, elimination of synapse during development, aberrant synapse pruning in neurologic disorders, damage to nerve cells in autoimmune diseases, and traumatic injury. Activation of the complement system in multiple sclerosis (MS) is typically thought to occur as part of a primary (auto)immune response from the periphery (the outside) against CNS antigens (the inside). However, evidence of local complement production from CNS-resident cells, intracellular complement functions, and the more recently discovered role of early complement components in shaping synaptic circuits in the absence of inflammation opens up the possibility that complement-related sequelae may start and finish within the brain itself. In this review, the complement system will be introduced, followed by evidence that implicates complement in shaping the developing, adult, and normal aging CNS as well as its contribution to pathology in neurodegenerative conditions. Discussion of data supporting “outside-in” vs. “inside-out” roles of complement in MS will be presented, concluded by thoughts on potential approaches to therapies targeting specific elements of the complement system.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Frontiers Media
ISSN: 1662-5102
Date of First Compliant Deposit: 26 January 2022
Date of Acceptance: 24 November 2020
Last Modified: 06 May 2023 05:25

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