Department of Nutrition and Biochemistry, Pontificia Universidad Javeriana, 110911 Bogota, Colombia.
Cells. 2020 Mar 31;9(4):846. doi: 10.3390/cells9040846.
Gap junction (GJ) channels and their connexins (Cxs) are complex proteins that have essential functions in cell communication processes in the central nervous system (CNS). Neurons, astrocytes, oligodendrocytes, and microglial cells express an extraordinary repertory of Cxs that are important for cell to cell communication and diffusion of metabolites, ions, neurotransmitters, and gliotransmitters. GJs and Cxs not only contribute to the normal function of the CNS but also the pathological progress of several diseases, such as cancer and neurodegenerative diseases. Besides, they have important roles in mediating neuroprotection by internal or external molecules. However, regulation of Cx expression by epigenetic mechanisms has not been fully elucidated. In this review, we provide an overview of the known mechanisms that regulate the expression of the most abundant Cxs in the central nervous system, Cx30, Cx36, and Cx43, and their role in brain cancer, CNS disorders, and neuroprotection. Initially, we focus on describing the Cx gene structure and how this is regulated by epigenetic mechanisms. Then, the posttranslational modifications that mediate the activity and stability of Cxs are reviewed. Finally, the role of GJs and Cxs in glioblastoma, Alzheimer's, Parkinson's, and Huntington's diseases, and neuroprotection are analyzed with the aim of shedding light in the possibility of using Cx regulators as potential therapeutic molecules.
间隙连接 (GJ) 通道及其连接蛋白 (Cx) 是复杂的蛋白质，在中枢神经系统 (CNS) 的细胞通讯过程中具有重要功能。神经元、星形胶质细胞、少突胶质细胞和小胶质细胞表达了丰富的 Cx，这些 Cx 对于细胞间通讯以及代谢物、离子、神经递质和Gliotransmitters 的扩散非常重要。GJ 和 Cx 不仅有助于 CNS 的正常功能，而且有助于多种疾病（如癌症和神经退行性疾病）的病理进展。此外，它们在介导内源性或外源性分子的神经保护方面也起着重要作用。然而，Cx 表达的表观遗传调控机制尚未完全阐明。在这篇综述中，我们概述了调节中枢神经系统中最丰富的 Cx（Cx30、Cx36 和 Cx43）表达的已知机制，及其在脑癌、CNS 疾病和神经保护中的作用。首先，我们重点描述 Cx 基因结构以及它如何受表观遗传机制调控。然后，我们回顾了介导 Cx 活性和稳定性的翻译后修饰。最后，分析了 GJ 和 Cx 在神经胶质瘤、阿尔茨海默病、帕金森病和亨廷顿病以及神经保护中的作用，以期揭示 Cx 调节剂作为潜在治疗分子的可能性。
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