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电压门控钙通道在基底神经节神经退行性疾病中的作用。

The Role of Voltage-Gated Calcium Channels in Basal Ganglia Neurodegenerative Disorders.

机构信息

Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Department of Pharmacology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

出版信息

Curr Neuropharmacol. 2023;21(2):183-201. doi: 10.2174/1570159X20666220327211156.

Abstract

Calcium (Ca) plays a central role in regulating many cellular processes and influences cell survival. Several mechanisms can disrupt Ca homeostasis to trigger cell death, including oxidative stress, mitochondrial damage, excitotoxicity, neuroinflammation, autophagy, and apoptosis. Voltage-gated Ca channels (VGCCs) act as the main source of Ca entry into electrically excitable cells, such as neurons, and they are also expressed in glial cells such as astrocytes and oligodendrocytes. The dysregulation of VGCC activity has been reported in both Parkinson's disease (PD) and Huntington's (HD). PD and HD are progressive neurodegenerative disorders (NDs) of the basal ganglia characterized by motor impairment as well as cognitive and psychiatric dysfunctions. This review will examine the putative role of neuronal VGCCs in the pathogenesis and treatment of central movement disorders, focusing on PD and HD. The link between basal ganglia disorders and VGCC physiology will provide a framework for understanding the neurodegenerative processes that occur in PD and HD, as well as a possible path towards identifying new therapeutic targets for the treatment of these debilitating disorders.

摘要

钙(Ca)在调节许多细胞过程中起着核心作用,并影响细胞存活。几种机制可以破坏 Ca 稳态,引发细胞死亡,包括氧化应激、线粒体损伤、兴奋性毒性、神经炎症、自噬和细胞凋亡。电压门控钙通道(VGCC)是进入电兴奋细胞(如神经元)的 Ca 进入的主要来源,也在神经胶质细胞(如星形胶质细胞和少突胶质细胞)中表达。VGCC 活性的失调已在帕金森病(PD)和亨廷顿病(HD)中报道。PD 和 HD 是基底神经节的进行性神经退行性疾病(NDs),其特征是运动障碍以及认知和精神功能障碍。本综述将探讨神经元 VGCC 在中枢运动障碍(重点是 PD 和 HD)发病机制和治疗中的潜在作用。基底神经节疾病与 VGCC 生理学之间的联系将为理解 PD 和 HD 中发生的神经退行性过程提供一个框架,并为这些使人衰弱的疾病的治疗确定新的治疗靶点提供可能的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569a/10190140/badac6caeb7c/CN-21-183_F1.jpg

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