Effects of α-Synuclein-Associated Post-Translational Modifications in Parkinson's Disease

被引：40
|
作者：
He, Songzhe [1 ,2 ,3 ]
Wang, Fushun [4 ,5 ]
Yung, Ken Kin Lam [6 ]
Zhang, Shiqing [6 ]
Qu, Shaogang [1 ,2 ,3 ]
机构：
[1] Southern Med Univ, Nanfang Hosp, Dept Neurol, Guangzhou 510515, Guangdong, Peoples R China
[2] Guangdong Hong Kong Macao Greater Bay Area Ctr Br, Guangzhou 510515, Guangdong, Peoples R China
[3] Southern Med Univ, Key Lab Mental Hlth, Minist Educ, Guangzhou 510515, Guangdong, Peoples R China
[4] Sichuan Normal Univ, Inst Brain & Psychol Sci, Chengdu 610066, Sichuan, Peoples R China
[5] Univ Rochester, Dept Neurosurg, Med Ctr, New York, NY 14643 USA
[6] Hong Kong Baptist Univ, Fac Sci, Dept Biol, Hong Kong 999077, Peoples R China
来源：
ACS CHEMICAL NEUROSCIENCE | 2021年 / 12卷 / 07期
基金：
中国国家自然科学基金;
关键词：
alpha-Synuclein; Parkinson's disease; protein misfolding; protein aggregation; post-translational modifications; neurodegenerative diseases; N-TERMINAL ACETYLATION; O-GLCNACYLATION; BLOOD-CELLS; AGGREGATION; PHOSPHORYLATION; PROTEIN; MUTATION; UBIQUITIN; TRUNCATION; OLIGOMERIZATION;
D O I：
10.1021/acschemneuro.1c00028
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
alpha-Synuclein (alpha-syn), a small highly conserved presynaptic protein containing 140 amino acids, is thought to be the main pathological hallmark in related neurodegenerative disorders. Although the normal function of alpha-syn is closely involved in the regulation of vesicular neurotransmission in these diseases, the underlying mechanisms of post-translational modifications (PTMs) of alpha-syn in the pathogenesis of Parkinson's disease (PD) have not been fully characterized. The pathological accumulation of misfolded alpha-syn has a critical role in PD pathogenesis. Recent studies of factors contributing to alpha-syn-associated aggregation and misfolding have expanded our understanding of the PD disease process. In this Review, we summarize the structure and physiological function of alpha-syn, and we further highlight the major PTMs (namely phosphorylation, ubiquitination, nitration, acetylation, truncation, SUMOylation, and O-GlcNAcylation) of alpha-syn and the effects of these modifications on alpha-syn aggregation, which may elucidate mechanisms for PD pathogenesis and lay a theoretical foundation for clinical treatment of PD.
引用
收藏
页码：1061 / 1071
页数：11
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