An “Outside-In” and “Inside-Out” Consideration of Complement in the Multiple Sclerosis Brain: Lessons From Development and Neurodegenerative Diseases

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