C5 and neurodegenerative disease: The majority of proinflammatory effects of C5a result from binding to the canonical G protein–coupled C5aR1 (19), and accumulating evidence has implicated an overproduction of C5a or overexpressed C5aR1 in the pathogenesis of many inflammatory conditions, autoimmune dysfunction, and neurodegenerative diseases (20, 21, 22, 23).