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

• Published in: Inflammation research Vol. 72; no. 3; pp. 443 - 462
• Main Authors: Lv, Qian-Kun, Tao, Kang-Xin, Wang, Xiao-Bo, Yao, Xiao-Yu, Pang, Meng-Zhu, Liu, Jun-Yi, Wang, Fen, Liu, Chun-Feng
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2023; Springer Nature B.V
• Subjects: Accumulation; Allergology; alpha-Synuclein - genetics; alpha-Synuclein - metabolism; Apoptosis; Autophagy; Biomedical and Life Sciences; Biomedicine; Dermatology; Homeostasis; Humans; Immunology; Inflammasomes; Inflammasomes - metabolism; Inflammation; LRRK2 protein; Microglia; Microglia - metabolism; Movement disorders; Neurodegenerative diseases; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Neuroinflammatory Diseases; Neurology; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; PARK7 protein; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Pathogenesis; Phagocytosis; Pharmacology/Toxicology; Phenotypes; Review; Rheumatology; Synuclein; α-Synuclein; Neuroinflammation; Autophagy; Phagocytosis; Microglia
• ISSN: 1023-3830; 1420-908X; 1420-908X
• DOI: 10.1007/s00011-022-01676-x

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.