Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, School of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Institute of Brain Science and Disease, Qingdao University, Qingdao, 266071, China.
Transl Neurodegener. 2021 Oct 18;10(1):39. doi: 10.1186/s40035-021-00265-y.
Parkinson's disease (PD) is a common neurodegenerative disorder that primarily affects the elderly. While the etiology of PD is likely multifactorial with the involvement of genetic, environmental, aging and other factors, α-synuclein (α-syn) pathology is a pivotal mechanism underlying the development of PD. In recent years, astrocytes have attracted considerable attention in the field. Although astrocytes perform a variety of physiological functions in the brain, they are pivotal mediators of α-syn toxicity since they internalize α-syn released from damaged neurons, and this triggers an inflammatory response, protein degradation dysfunction, mitochondrial dysfunction and endoplasmic reticulum stress. Astrocytes are indispensable coordinators in the background of several genetic mutations, including PARK7, GBA1, LRRK2, ATP13A2, PINK1, PRKN and PLA2G6. As the most abundant glial cells in the brain, functional astrocytes can be replenished and even converted to functional neurons. In this review, we discuss astrocyte dysfunction in PD with an emphasis on α-syn toxicity and genetic modulation and conclude that astrocyte replenishment is a valuable therapeutic approach in PD.
帕金森病（PD）是一种常见的神经退行性疾病，主要影响老年人。虽然 PD 的病因可能是多因素的，涉及遗传、环境、衰老和其他因素，但α-突触核蛋白（α-syn）病理学是 PD 发展的关键机制。近年来，星形胶质细胞在该领域引起了相当大的关注。尽管星形胶质细胞在大脑中执行多种生理功能，但它们是α-syn 毒性的关键介质，因为它们可以内化从受损神经元释放的α-syn，这会引发炎症反应、蛋白降解功能障碍、线粒体功能障碍和内质网应激。星形胶质细胞是包括 PARK7、GBA1、LRRK2、ATP13A2、PINK1、PRKN 和 PLA2G6 在内的几种基因突变背景中不可或缺的协调者。作为大脑中最丰富的神经胶质细胞，功能性星形胶质细胞可以被补充，甚至可以转化为功能性神经元。在这篇综述中，我们讨论了 PD 中的星形胶质细胞功能障碍，重点讨论了α-syn 毒性和遗传调节，并得出结论，星形胶质细胞补充是 PD 有价值的治疗方法。
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