Table_1_The Role of Glial Mitochondria in α-Synuclein Toxicity.DOCX

The abnormal accumulation of alpha-synuclein (α-syn) aggregates in neurons and glial cells is widely known to be associated with many neurodegenerative diseases, including Parkinson’s disease (PD), Dementia with Lewy bodies (DLB), and Multiple system atrophy (MSA). Mitochondrial dysfunction in neurons and glia is known as a key feature of α-syn toxicity. Studies aimed at understanding α-syn-induced toxicity and its role in neurodegenerative diseases have primarily focused on neurons. However, a growing body of evidence demonstrates that glial cells such as microglia and astrocytes have been implicated in the initial pathogenesis and the progression of α-Synucleinopathy. Glial cells are important for supporting neuronal survival, synaptic functions, and local immunity. Furthermore, recent studies highlight the role of mitochondrial metabolism in the normal function of glial cells. In this work, we review the complex relationship between glial mitochondria and α-syn-mediated neurodegeneration, which may provide novel insights into the roles of glial cells in α-syn-associated neurodegenerative diseases.

神经元与神经胶质细胞内α-突触核蛋白（alpha-synuclein，α-syn）聚集体的异常蓄积，已被广泛证实与多种神经退行性疾病相关，包括帕金森病（Parkinson’s disease，PD）、路易体痴呆（Dementia with Lewy bodies，DLB）以及多系统萎缩（Multiple system atrophy，MSA）。神经元与胶质细胞的线粒体功能障碍，是α-syn毒性作用的关键特征。以往旨在解析α-syn诱导的毒性及其在神经退行性疾病中作用的研究，主要以神经元为研究对象。然而，越来越多的研究证据表明，小胶质细胞（microglia）、星形胶质细胞（astrocytes）等胶质细胞，参与了α-突触核蛋白病（α-Synucleinopathy）的初始发病过程与疾病进展。胶质细胞对于维持神经元存活、突触功能以及局部免疫稳态具有重要作用。此外，近期研究进一步凸显了线粒体代谢在胶质细胞正常生理功能中的关键作用。本综述探讨了胶质细胞线粒体与α-syn介导的神经退行性变之间的复杂关联，有望为阐明胶质细胞在α-syn相关神经退行性疾病中的作用提供全新视角。