FirstString Research, Inc., 300 W. Coleman Blvd., Suite 203, Mount Pleasant, SC, United States.
Department of Surgery, Division of General Surgery, Medical University of South Carolina, Charleston, SC, United States.
FEBS Lett. 2014 Apr 17;588(8):1349-64. doi: 10.1016/j.febslet.2014.02.047. Epub 2014 Mar 4.
Gap junctions and their connexin components are indispensable in mediating the cellular coordination required for tissue and organ homeostasis. The critical nature of their existence mandates a connection to disease while at the same time offering therapeutic potential. Therapeutic intervention may be offered through the pharmacological and molecular disruption of the pathways involved in connexin biosynthesis, gap junction assembly, stabilization, or degradation. Chemical inhibitors aimed at closing connexin channels, peptide mimetics corresponding to short connexin sequences, and gene therapy approaches have been incredibly useful molecular tools in deciphering the complexities associated with connexin biology. Recently, therapeutic potential in targeting connexins has evolved from basic research in cell-based models to clinical opportunity in the form of human trials. Clinical promise is particularly evident with regards to targeting connexin43 in the context of wound healing. The following review is aimed at highlighting novel advances where the pharmacological manipulation of connexin biology has proven beneficial in animals or humans.
间隙连接及其连接蛋白在介导组织和器官稳态所需的细胞协调中不可或缺。它们的存在至关重要,与疾病有关,同时也具有治疗潜力。治疗干预可以通过药理学和分子手段来破坏连接蛋白生物合成、间隙连接组装、稳定或降解所涉及的途径。旨在关闭连接蛋白通道的化学抑制剂、对应于短连接蛋白序列的肽模拟物以及基因治疗方法,已成为解析连接蛋白生物学相关复杂性的非常有用的分子工具。最近,针对连接蛋白的治疗潜力已经从基于细胞模型的基础研究发展到临床试验的形式。在创伤愈合的背景下靶向连接蛋白 43 方面,临床前景尤为明显。以下综述旨在强调在动物或人类中,连接蛋白生物学的药理学干预已被证明是有益的新进展。