Baracaldo-Santamaría Daniela, Corrales-Hernández María Gabriela, Ortiz-Vergara Maria Camila, Cormane-Alfaro Valeria, Luque-Bernal Ricardo-Miguel, Calderon-Ospina Carlos-Alberto, Cediel-Becerra Juan-Fernando
Pharmacology Unit, Department of Biomedical Sciences, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, Colombia.
Anatomy and Embriology Units, Department of Biomedical Sciences, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, Colombia.
Biomedicines. 2022 Sep 9;10(9):2237. doi: 10.3390/biomedicines10092237.
Cell-to-cell communication is essential for proper embryonic development and its dysfunction may lead to disease. Recent research has drawn attention to a new group of molecules called connexins (Cxs) and pannexins (Panxs). Cxs have been described for more than forty years as pivotal regulators of embryogenesis; however, the exact mechanism by which they provide this regulation has not been clearly elucidated. Consequently, Cxs and Panxs have been linked to congenital neurodegenerative diseases such as Charcot-Marie-Tooth disease and, more recently, chronic hemichannel opening has been associated with adult neurodegenerative diseases (e.g., Alzheimer's disease). Cell-to-cell communication via gap junctions formed by hexameric assemblies of Cxs, known as connexons, is believed to be a crucial component in developmental regulation. As for Panxs, despite being topologically similar to Cxs, they predominantly seem to form channels connecting the cytoplasm to the extracellular space and, despite recent research into Panx1 (Pannexin 1) expression in different regions of the brain during the embryonic phase, it has been studied to a lesser degree. When it comes to the nervous system, Cxs and Panxs play an important role in early stages of neuronal development with a wide span of action ranging from cellular migration during early stages to neuronal differentiation and system circuitry formation. In this review, we describe the most recent available evidence regarding the molecular and structural aspects of Cx and Panx channels, their role in neurodevelopment, congenital and adult neurological diseases, and finally propose how pharmacological modulation of these channels could modify the pathogenesis of some diseases.
细胞间通讯对于胚胎正常发育至关重要，其功能失调可能导致疾病。最近的研究已将注意力转向一类名为连接蛋白（Cxs）和泛连接蛋白（Panxs）的新分子。四十多年来，Cxs一直被描述为胚胎发育的关键调节因子；然而，它们提供这种调节的确切机制尚未完全阐明。因此，Cxs和Panxs与诸如夏科-马里-图斯病等先天性神经退行性疾病有关，并且最近慢性半通道开放已与成人神经退行性疾病（如阿尔茨海默病）相关联。通过由Cxs的六聚体组装形成的缝隙连接进行的细胞间通讯，即连接子，被认为是发育调节中的关键组成部分。至于Panxs，尽管在拓扑结构上与Cxs相似，但它们似乎主要形成连接细胞质与细胞外空间的通道，并且尽管最近对胚胎期大脑不同区域中Panx1（泛连接蛋白1）的表达进行了研究，但其研究程度较低。在神经系统中，Cxs和Panxs在神经元发育的早期阶段发挥重要作用，其作用范围广泛，从早期的细胞迁移到神经元分化和系统电路形成。在这篇综述中，我们描述了关于Cx和Panx通道的分子和结构方面的最新可用证据、它们在神经发育、先天性和成人神经系统疾病中的作用，最后提出对这些通道的药理学调节如何能够改变某些疾病的发病机制。
