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Review
. 2023 Mar;72(3):443-462.
doi: 10.1007/s00011-022-01676-x. Epub 2023 Jan 4.

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

Qian-Kun Lv  1   2 , Kang-Xin Tao  2 , Xiao-Bo Wang  2 , Xiao-Yu Yao  1   2 , Meng-Zhu Pang  2 , Jun-Yi Liu  3 , Fen Wang  4   5 , Chun-Feng Liu  6   7
Affiliations
Review

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

Qian-Kun Lv et al. Inflamm Res. 2023 Mar.

Abstract

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease, and is characterized by accumulation of α-synuclein (α-syn). Neuroinflammation driven by microglia is an important pathological manifestation of PD. α-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 α-syn and NLRP3 inflammasome blockage to relieve neuroinflammation. Microglial autophagy and phagocytosis of released α-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 α-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 α-syn in PD pathogenesis and the possible mechanism of microglial autophagy and phagocytosis in α-syn clearance and inhibition of neuroinflammation. This may provide a novel insight into treatment of PD.

Keywords: Autophagy; Microglia; Neuroinflammation; Phagocytosis; α-Synuclein.

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