TY - JOUR
T1 - Effects of α-Synuclein-Associated Post-Translational Modifications in Parkinson's Disease
AU - He, Songzhe
AU - Wang, Fushun
AU - Yung, Kin Lam
AU - Zhang, Shiqing
AU - Qu, Shaogang
N1 - Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (U1603281 and 81870991), and the key innovational technology project of Guangzhou (2018-1202-SF-0019).
Publisher Copyright:
©
PY - 2021/4/7
Y1 - 2021/4/7
N2 - α-Synuclein (α-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 α-syn is closely involved in the regulation of vesicular neurotransmission in these diseases, the underlying mechanisms of post-translational modifications (PTMs) of α-syn in the pathogenesis of Parkinson's disease (PD) have not been fully characterized. The pathological accumulation of misfolded α-syn has a critical role in PD pathogenesis. Recent studies of factors contributing to α-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 α-syn, and we further highlight the major PTMs (namely phosphorylation, ubiquitination, nitration, acetylation, truncation, SUMOylation, and O-GlcNAcylation) of α-syn and the effects of these modifications on α-syn aggregation, which may elucidate mechanisms for PD pathogenesis and lay a theoretical foundation for clinical treatment of PD.
AB - α-Synuclein (α-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 α-syn is closely involved in the regulation of vesicular neurotransmission in these diseases, the underlying mechanisms of post-translational modifications (PTMs) of α-syn in the pathogenesis of Parkinson's disease (PD) have not been fully characterized. The pathological accumulation of misfolded α-syn has a critical role in PD pathogenesis. Recent studies of factors contributing to α-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 α-syn, and we further highlight the major PTMs (namely phosphorylation, ubiquitination, nitration, acetylation, truncation, SUMOylation, and O-GlcNAcylation) of α-syn and the effects of these modifications on α-syn aggregation, which may elucidate mechanisms for PD pathogenesis and lay a theoretical foundation for clinical treatment of PD.
KW - neurodegenerative diseases
KW - Parkinson's disease
KW - post-translational modifications
KW - protein aggregation
KW - protein misfolding
KW - α-Synuclein
UR - http://www.scopus.com/inward/record.url?scp=85104047000&partnerID=8YFLogxK
U2 - 10.1021/acschemneuro.1c00028
DO - 10.1021/acschemneuro.1c00028
M3 - Review article
C2 - 33769791
AN - SCOPUS:85104047000
SN - 1948-7193
VL - 12
SP - 1061
EP - 1071
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
IS - 7
ER -