Huang Xiaomin, Su Yixun, Wang Nan, Li Hui, Li Zhigang, Yin Guowei, Chen Hui, Niu Jianqin, Yi Chenju
Research Centre, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
School of Life Sciences, University of Technology Sydney, Sydney, NSW, Australia.
Front Mol Neurosci. 2021 May 28;14:657514. doi: 10.3389/fnmol.2021.657514. eCollection 2021.
Astrocytes play a crucial role in the maintenance of the normal functions of the Central Nervous System (CNS). During the pathogenesis of neurodegenerative diseases, astrocytes undergo morphological and functional remodeling, a process called reactive astrogliosis, in response to the insults to the CNS. One of the key aspects of the reactive astrocytes is the change in the expression and function of connexins. Connexins are channel proteins that highly expressed in astrocytes, forming gap junction channels and hemichannels, allowing diffusional trafficking of small molecules. Alterations of astrocytic connexin expression and function found in neurodegenerative diseases have been shown to affect the disease progression by changing neuronal function and survival. In this review, we will summarize the role of astroglial connexins in neurodegenerative diseases including Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Also, we will discuss why targeting connexins can be a plausible therapeutic strategy to manage these neurodegenerative diseases.
星形胶质细胞在维持中枢神经系统(CNS)的正常功能中起着至关重要的作用。在神经退行性疾病的发病过程中,星形胶质细胞会发生形态和功能重塑,这一过程称为反应性星形胶质细胞增生,以应对中枢神经系统受到的损伤。反应性星形胶质细胞的一个关键方面是连接蛋白的表达和功能发生变化。连接蛋白是在星形胶质细胞中高度表达的通道蛋白,形成间隙连接通道和半通道,允许小分子进行扩散运输。在神经退行性疾病中发现的星形胶质细胞连接蛋白表达和功能的改变已被证明会通过改变神经元功能和存活来影响疾病进展。在这篇综述中,我们将总结星形胶质细胞连接蛋白在包括阿尔茨海默病、亨廷顿舞蹈病、帕金森病和肌萎缩侧索硬化症在内的神经退行性疾病中的作用。此外,我们还将讨论为什么靶向连接蛋白可能是治疗这些神经退行性疾病的一种可行策略。