Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, Guangdong 510515, China.
ACS Chem Neurosci. 2021 Apr 7;12(7):1061-1071. doi: 10.1021/acschemneuro.1c00028. Epub 2021 Mar 26.
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.
α-突触核蛋白（α-syn）是一种小而高度保守的突触前蛋白，包含 140 个氨基酸，被认为是相关神经退行性疾病的主要病理标志。虽然 α-syn 的正常功能与这些疾病中囊泡神经递质传递的调节密切相关，但帕金森病（PD）发病机制中 α-syn 的翻译后修饰（PTMs）的潜在机制尚未完全阐明。错误折叠的 α-syn 的病理性积累在 PD 的发病机制中起着关键作用。最近对导致 α-syn 相关聚集和错误折叠的因素的研究扩展了我们对 PD 疾病过程的理解。在这篇综述中，我们总结了 α-syn 的结构和生理功能，并且进一步强调了 α-syn 的主要 PTMs（即磷酸化、泛素化、硝化、乙酰化、截断、SUMO 化和 O-GlcNAc 化）及其对 α-syn 聚集的影响，这可能阐明 PD 发病机制的机制，并为 PD 的临床治疗奠定理论基础。
