Center of Translational Medicine, First People's Hospital of Taicang, Taicang Affiliated Hospital of Soochow University, Suzhou, 215400, China.
Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Neurosci Bull. 2023 Mar;39(3):479-490. doi: 10.1007/s12264-022-00957-z. Epub 2022 Oct 14.
The accumulation of pathological α-synuclein (α-syn) in the central nervous system and the progressive loss of dopaminergic neurons in the substantia nigra pars compacta are the neuropathological features of Parkinson's disease (PD). Recently, the findings of prion-like transmission of α-syn pathology have expanded our understanding of the region-specific distribution of α-syn in PD patients. Accumulating evidence suggests that α-syn aggregates are released from neurons and endocytosed by glial cells, which contributes to the clearance of α-syn. However, the activation of glial cells by α-syn species produces pro-inflammatory factors that decrease the uptake of α-syn aggregates by glial cells and promote the transmission of α-syn between neurons, which promotes the spread of α-syn pathology. In this article, we provide an overview of current knowledge on the role of glia and α-syn pathology in PD pathogenesis, highlighting the relationships between glial responses and the spread of α-syn pathology.
在帕金森病（PD）中，病理性α-突触核蛋白（α-syn）在中枢神经系统中的积累和黑质致密部多巴胺能神经元的进行性丧失是其神经病理学特征。最近，α-syn 病理学的朊病毒样传播的发现扩展了我们对 PD 患者中 α-syn 区域特异性分布的认识。越来越多的证据表明，α-syn 聚集物从神经元中释放出来并被神经胶质细胞内吞，这有助于清除 α-syn。然而，α-syn 物种激活神经胶质细胞产生促炎因子，减少神经胶质细胞对 α-syn 聚集物的摄取，并促进 α-syn 在神经元之间的传递，从而促进 α-syn 病理学的传播。在本文中，我们概述了目前关于胶质细胞和 α-syn 病理学在 PD 发病机制中的作用的知识，强调了胶质细胞反应与 α-syn 病理学传播之间的关系。
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