Tonkin Ryan S, Mao Yilin, O'Carroll Simon J, Nicholson Louise F B, Green Colin R, Gorrie Catherine A, Moalem-Taylor Gila
School of Medical Sciences, Faculty of Medicine, University of New South Wales Sydney, NSW, Australia.
School of Medical and Molecular Bioscience, Faculty of Science, University of Technology Sydney, NSW, Australia.
Front Mol Neurosci. 2015 Jan 6;7:102. doi: 10.3389/fnmol.2014.00102. eCollection 2014.
Gap junctions are specialized intercellular communication channels that are formed by two hexameric connexin hemichannels, one provided by each of the two adjacent cells. Gap junctions and hemichannels play an important role in regulating cellular metabolism, signaling, and functions in both normal and pathological conditions. Following spinal cord injury (SCI), there is damage and disturbance to the neuronal elements of the spinal cord including severing of axon tracts and rapid cell death. The initial mechanical disruption is followed by multiple secondary cascades that cause further tissue loss and dysfunction. Recent studies have implicated connexin proteins as playing a critical role in the secondary phase of SCI by propagating death signals through extensive glial networks. In this review, we bring together past and current studies to outline the distribution, changes and roles of various connexins found in neurons and glial cells, before and in response to SCI. We discuss the contribution of pathologically activated connexin proteins, in particular connexin 43, to functional recovery and neuropathic pain, as well as providing an update on potential connexin specific pharmacological agents to treat SCI.
缝隙连接是一种特殊的细胞间通讯通道，由两个六聚体连接蛋白半通道形成，两个相邻细胞各提供一个。缝隙连接和半通道在正常和病理条件下调节细胞代谢、信号传导及功能方面发挥着重要作用。脊髓损伤（SCI）后，脊髓的神经元成分会受到损伤和干扰，包括轴突束的切断和细胞快速死亡。最初的机械性破坏之后会引发多个继发性级联反应，导致进一步的组织损失和功能障碍。最近的研究表明，连接蛋白通过广泛的胶质网络传播死亡信号，在脊髓损伤的继发阶段发挥关键作用。在这篇综述中，我们汇总了过去和当前的研究，以概述在脊髓损伤之前以及损伤后，神经元和胶质细胞中发现的各种连接蛋白的分布、变化及作用。我们讨论了病理激活的连接蛋白，特别是连接蛋白43对功能恢复和神经性疼痛的影响，以及介绍了用于治疗脊髓损伤的潜在连接蛋白特异性药物的最新情况。
