Role of alpha-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson's disease

Background Parkinson's disease (PD) is the second most common neurodegenerative disease, and is characterized by accumulation of alpha-synuclein (alpha-syn). Neuroinflammation driven by microglia is an important pathological manifestation of PD. alpha-Syn is a crucial marker of PD, and its accumulation leads to microglia M1-like phenotype polarization, activation of NLRP3 inflammasomes, and impaired autophagy and phagocytosis in microglia. Autophagy of microglia is related to degradation of alpha-syn and NLRP3 inflammasome blockage to relieve neuroinflammation. Microglial autophagy and phagocytosis of released alpha-syn or fragments from apoptotic neurons maintain homeostasis in the brain. A variety of PD-related genes such as LRRK2, GBA and DJ-1 also contribute to this stability process. Objectives Further studies are needed to determine how alpha-syn works in microglia. Methods A keyword-based search was performed using the PubMed database for published articles. Conclusion In this review, we discuss the interaction between microglia and alpha-syn in PD pathogenesis and the possible mechanism of microglial autophagy and phagocytosis in alpha-syn clearance and inhibition of neuroinflammation. This may provide a novel insight into treatment of PD.

Automated summary

Parkinson's disease is a common neurodegenerative disease characterized by the accumulation of alpha-synuclein in microglia, leading to neuroinflammation. The autophagy and phagocytosis functions of microglia are related to the clearance of alpha-synuclein and the inhibition of neuroinflammation. This review discusses the interaction between microglia and alpha-synuclein in Parkinson's disease pathogenesis, and the possible mechanisms of microglial autophagy and phagocytosis in the clearance of alpha-synuclein and inhibition of neuroinflammation.