当前位置: X-MOL 学术Curr. Opin. Pharmacol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
TMEM16A (ANO1) as a therapeutic target in cystic fibrosis
Current Opinion in Pharmacology ( IF 4 ) Pub Date : 2022-03-29 , DOI: 10.1016/j.coph.2022.102206
Luis J V Galietta 1
Affiliation  

Cystic fibrosis (CF) is a multi-organ genetic disease caused by loss of function of CFTR, a cAMP-regulated chloride channel expressed in epithelial cells. In airway epithelia, CFTR-dependent chloride secretion is required to humidify mucosal surface and to allow efficient mucociliary clearance. In CF patients, CFTR deficit causes chronic bacterial infections and airway obstruction by mucus accumulation. Airway epithelial cells also express TMEM16A (ANO1), a second type of chloride channel, whose activity is controlled by cytosolic calcium concentration. Pharmacological stimulation of TMEM16A could be beneficial to bypass CFTR defect. However, the relationship of TMEM16A with mucus hypersecretion needs to be clarified. Multiple large scale screenings have been carried out to identify inhibitors and activators/potentiators of TMEM16A, including CaCCinh-A01, T16inh-A01, Ani9, TMinh-23, MONNA, Eact, and ETX001. Such compounds are important as research tools, to assess the role of TMEM16A in health and disease, and as possible therapeutic agents.



中文翻译:

TMEM16A (ANO1) 作为囊性纤维化的治疗靶点

囊性纤维化 (CF) 是由 CFTR 功能丧失引起的多器官遗传疾病,CFTR 是一种在上皮细胞中表达的 cAMP 调节的氯离子通道。在气道上皮细胞中,需要 CFTR 依赖性氯化物分泌来润湿粘膜表面并允许有效的粘膜纤毛清除。在 CF 患者中,CFTR 缺乏导致粘液积聚导致慢性细菌感染和气道阻塞。气道上皮细胞也表达 TMEM16A (ANO1),这是第二种氯离子通道,其活性受胞质钙浓度控制。TMEM16A 的药理刺激可能有益于绕过 CFTR 缺陷。然而,需要澄清 TMEM16A 与粘液分泌过多的关系。已经进行了多次大规模筛选以鉴定 TMEM16A 的抑制剂和激活剂/增强剂,包括 CaCCinh -A01、T16 inh -A01、Ani9、TM inh -23、MONNA、E act和 ETX001。这些化合物作为研究工具很重要,可以评估 TMEM16A 在健康和疾病中的作用,也可以作为可能的治疗剂。

更新日期:2022-03-29
down
wechat
bug