CFTR: a missing link between exocrine and endocrine pancreas?

作     者：HWANG Tzyh-Chang 

作者机构：Department of Medical Pharmacology and Physiology Dalton Cardiovascular Research Center University of Missouri 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2014年第57卷第10期

页      面：1044-1045页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：National Institute of Diabetes and Digestive and Kidney Diseases NIDDK: R01DK055835 

主　　题：内分泌 遗传性疾病 阴离子通道 基因突变 胰腺 上皮细胞 苯丙氨酸 等位基因 

摘      要：Cystic fibrosis （CF）, a life-shortening hereditary disease mainly afflicting people of Caucasian origins, is caused by loss-of-function mutations in the CFTR （Cystic Fibrosis Transmembrane conductance Regulator） gene, which encodes a phosphorylation-activated, but ATP-gated anion channel expressed primarily in epithelial cells. To date, nearly 2000 mutations have been identified as pathogenic, but the deletion of a single amino acid phenylalanine at position 508 （i.e., deltaF508） accounts for -70% of all disease-associated mutations and thus is present in at least one allele of -90% of patients with CF, This mutation not only decreases the number of functional CFTR molecules in the plasma membrane due to defective folding of the deltaF508-CFTR protein, but also disrupts ATP-dependent opening and closing （or gating） of the CFTR channel for the minor fraction of deltaF508-CFTR channels that do reach and stay in the cell membrane. While currently there is no cure for this debilitating disease, in the past decades, tremendous efforts have been committed to developing rea- gents that may help CFTR folding （i.e., correctors） or gating （i.e., potentiators）. Recent successes in the discovery of an effective CFTR potentiator VX-770 （or Ivacaftor） and in its subsequent clinical trials not only establish an important precedent for realizing personalized medicine but also may serve as a stepping-stone for attaining the eventual goal of curing CF.