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

被引：57
作者：
Lv, Qian-Kun [1 ,2 ,3 ,4 ]
Tao, Kang-Xin [3 ,4 ]
Wang, Xiao-Bo [3 ,4 ]
Yao, Xiao-Yu [1 ,2 ,3 ,4 ]
Pang, Meng-Zhu [3 ,4 ]
Liu, Jun-Yi [5 ]
Wang, Fen [1 ,2 ,3 ,4 ]
Liu, Chun-Feng [1 ,2 ,3 ,4 ]
机构：
[1] Soochow Univ, Dept Neurol, Affiliated Hosp 2, Suzhou 215004, Peoples R China
[2] Soochow Univ, Clin Res Ctr Neurol Dis, Affiliated Hosp 2, Suzhou 215004, Peoples R China
[3] Soochow Univ, Jiangsu Key Lab Neuropsychiat Dis, Suzhou 215123, Peoples R China
[4] Soochow Univ, Inst Neurosci, Suzhou 215123, Peoples R China
[5] Soochow Univ, Dept Neurol, Dushu Lake Hosp, Suzhou, Peoples R China
来源：
INFLAMMATION RESEARCH | 2023年 / 72卷 / 03期
基金：
中国国家自然科学基金;
关键词：
Microglia; alpha-Synuclein; Autophagy; Phagocytosis; Neuroinflammation; NLRP3 INFLAMMASOME ACTIVATION; CENTRAL-NERVOUS-SYSTEM; NADPH-OXIDASE; DOPAMINERGIC NEURODEGENERATION; CELL-CULTURE; MOUSE MODEL; RECEPTOR; RISK LOCI; BRAIN; INHIBITION;
D O I：
10.1007/s00011-022-01676-x
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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.
引用
收藏
页码：443 / 462
页数：20
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