School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Department of Pediatrics, University Hospital Heidelberg, Heidelberg, Germany; Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.
Curr Opin Pharmacol. 2017 Jun;34:91-97. doi: 10.1016/j.coph.2017.10.002. Epub 2017 Oct 21.
One therapeutic strategy for cystic fibrosis (CF) seeks to restore anion transport to affected epithelia by targeting other apical membrane Cl channels to bypass dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl channel. The properties and regulation of the Ca-activated Cl channel TMEM16A argue that long-acting small molecules which target directly TMEM16A are required to overcome CFTR loss. Through genetic studies of lung diseases, SLC26A9, a member of the solute carrier 26 family of anion transporters, has emerged as a promising target to bypass CFTR dysfunction. An alternative strategy to circumvent CFTR dysfunction is to deliver to CF epithelia artificial anion transporters that shuttle Cl across the apical membrane. Recently, powerful, non-toxic, biologically-active artificial anion transporters have emerged.
一种囊性纤维化 (CF) 的治疗策略是通过靶向其他顶端膜 Cl 通道来恢复受影响上皮的阴离子转运，从而绕过囊性纤维化跨膜电导调节剂 (CFTR) Cl 通道的功能障碍。钙激活 Cl 通道 TMEM16A 的特性和调节表明，需要针对 TMEM16A 的长效小分子来克服 CFTR 的缺失。通过对肺部疾病的遗传研究，溶质载体 26 家族的阴离子转运体 SLC26A9 作为绕过 CFTR 功能障碍的有希望的靶点出现。规避 CFTR 功能障碍的另一种策略是向 CF 上皮细胞输送穿过顶端膜穿梭 Cl 的人工阴离子转运体。最近，出现了强大、无毒、生物活性的人工阴离子转运体。
