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连接蛋白43半通道与相关疾病

Connexin 43 hemichannels and related diseases.

作者信息

Zhang Yanfeng, Acosta Francisca M, Jiang Jean X

机构信息

AlaMab Therapeutics Inc, 302 Carnegie Center Dr Suite 100, Princeton, NJ 08540, United States.

Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, United States.

出版信息

Antib Ther. 2024 Nov 11;7(4):361-369. doi: 10.1093/abt/tbae024. eCollection 2024 Oct.

Abstract

Connexin 43 (Cx43) protein forms hemichannels (connexons) and gap junctions, with hemichannels consisting of six Cx43 molecules and gap junctions formed by two hemichannels. While gap junctions are prevalent in organs like the heart and liver, hemichannels are found in specific cell types, such as astrocytes and osteocytes. They allow the passage of small molecules (<1.5 kDa) between the cytoplasm and extracellular matrix. Cx43 hemichannels have emerged as potential therapeutic targets in various diseases, including central nervous system disorders, bone-related diseases, diabetic complications, wound healing, and cancers. Aberrant hemichannel opening can worsen conditions by releasing inflammatory elements, such as causing gliosis in neuronal cells. Conversely, functional hemichannels may inhibit cancer cell growth and metastasis. Recent studies are revealing new mechanisms of Cx43 hemichannels, broadening their therapeutic applications and highlighting the importance of regulating their activity for improved disease outcomes.

摘要

连接蛋白43(Cx43)形成半通道(连接子)和间隙连接,半通道由六个Cx43分子组成,间隙连接则由两个半通道形成。虽然间隙连接在心脏和肝脏等器官中普遍存在,但半通道存在于特定的细胞类型中,如星形胶质细胞和骨细胞。它们允许小分子(<1.5 kDa)在细胞质和细胞外基质之间通过。Cx43半通道已成为包括中枢神经系统疾病、骨相关疾病、糖尿病并发症、伤口愈合和癌症在内的各种疾病的潜在治疗靶点。异常的半通道开放会通过释放炎症因子使病情恶化,比如在神经元细胞中引起胶质增生。相反,功能性半通道可能会抑制癌细胞的生长和转移。最近的研究揭示了Cx43半通道的新机制,拓宽了它们的治疗应用,并突出了调节其活性以改善疾病预后的重要性。

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