Freitas-Andrade M, Naus C C
Department of Cellular and Physiological Sciences, The Life Science Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Cellular and Physiological Sciences, The Life Science Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Neuroscience. 2016 May 26;323:207-21. doi: 10.1016/j.neuroscience.2015.04.035. Epub 2015 Apr 23.
The World Health Organization has predicted that by 2040 neurodegenerative diseases will overtake cancer to become the world's second leading cause of death after cardiovascular disease. This has sparked the development of several European and American brain research initiatives focusing on elucidating the underlying cellular and molecular mechanisms of neurodegenerative diseases. Connexin (Cx) and pannexin (Panx) membrane channel proteins are conduits through which neuronal, glial, and vascular tissues interact. In the brain, this interaction is highly critical for homeostasis and brain repair after injury. Understanding the molecular mechanisms by which these membrane channels function, in health and disease, might be particularly influential in establishing conceptual frameworks to develop new therapeutics against Cx and Panx channels. This review focuses on current insights and emerging concepts, particularly the impact of connexin43 and pannexin1, under neuroprotective and neurodegenerative conditions within the context of astrocytes.
世界卫生组织预测,到2040年,神经退行性疾病将超过癌症,成为仅次于心血管疾病的全球第二大死因。这引发了欧美多项脑研究计划的开展,这些计划聚焦于阐明神经退行性疾病潜在的细胞和分子机制。连接蛋白(Cx)和泛连接蛋白(Panx)膜通道蛋白是神经元、神经胶质和血管组织相互作用的通道。在大脑中,这种相互作用对于内环境稳定和损伤后的脑修复至关重要。了解这些膜通道在健康和疾病状态下发挥功能的分子机制,对于建立开发针对Cx和Panx通道的新疗法的概念框架可能具有特别重要的影响。本综述重点关注当前的见解和新兴概念,特别是在星形胶质细胞背景下,连接蛋白43和泛连接蛋白1在神经保护和神经退行性疾病状态下的影响。