Neuroprotective versus Neuroinflammatory Roles of Complement: From Development to Disease

Complement proteins are ancient components of innate immunity that have emerged as crucial regulators of neural networks. We discuss these roles in the context of the CNS development, acute CNS viral infections, and post-infectious and noninfectious CNS disorders, with an emphasis on microglia-mediated loss of synapses. Despite extensive examples that implicate classical complement proteins and their receptors in CNS dysfunction, recent data suggest that they exert neuroprotective roles in CNS homeostasis through continued refinement of synaptic connections. Thorough understanding of the mechanisms involved in these processes may lead to novel targets for the treatment of CNS diseases involving aberrant complement-mediated synapse loss.