Complement cascade functions during brain development and neurodegeneration

The complement system, an essential tightly regulated innate immune system, is a key regulator of normal central nervous system (CNS) development and function. However, aberrant complement component expression and activation in the brain may culminate into marked neuroinflammatory response, neurodegenerative processes and cognitive impairment. Over the years, complement-mediated neuroinflammatory responses and complement-driven neurodegeneration have been increasingly implicated in the pathogenesis of a wide spectrum of CNS disorders. This review describes how complement system contributes to normal brain development and function. We also discuss how pathologic insults such as misfolded proteins, lipid droplet/lipid droplet-associated protein or glycosaminoglycan accumulation could trigger complement-mediated neuroinflammatory responses and neurodegenerative process in neurodegenerative proteinopathies, age-related macular degeneration and neurodegenerative lysosomal storage disorders.