Let's make microglia great again in neurodegenerative disorders

All of the common neurodegenerative disorders-Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and prion diseases-are characterized by accumulation of misfolded proteins that trigger activation of microglia; brain-resident mononuclear phagocytes. This chronic form of neuroinflammation is earmarked by increased release of myriad cytokines and chemokines in patient brains and biofluids. Microglial phagocytosis is compromised early in the disease process, obfuscating clearance of abnormal proteins. This review identifies immune pathologies shared by the major neurodegenerative disorders. The overarching concept is that aberrant innate immune pathways can be targeted for return to homeostasis in hopes of coaxing microglia into clearing neurotoxic misfolded proteins.