Cystic fibrosis transmembrane regulator correctors and potentiators.
Cystic fibrosis transmembrane regulator correctors and potentiators.
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DOI：
10.1101/cshperspect.a009761
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发表时间：
2013-07-01
影响因子：
5.4
通讯作者：
Verkman AS
中科院分区：
文献类型：
--
作者：
Rowe SM;Verkman AS
囊性纤维化（CF）是由CF跨膜传导调节蛋白（CFTR）的功能缺失突变引起的，CFTR是一种camp调节的阴离子通道，主要表达于分泌上皮的顶质膜。近2000个CFTR基因突变已被确定，这些突变通过损害其翻译、细胞加工和/或氯离子通道门控而导致疾病。CFTR校正剂和增强剂治疗CF的基本前提是，通过解决CF的基本缺陷，解决导致CF的突变CFTR等位基因在细胞加工和氯离子通道功能中的潜在缺陷，将带来临床益处。校正剂主要针对F508del细胞错误加工，而增强剂旨在恢复突变CFTR细胞表面camp依赖性氯离子通道活性。本文综述了CFTR增强剂和校正剂的发现、已知的机理基础以及在临床试验中取得的令人鼓舞的结果。
Cystic fibrosis (CF) is caused by loss-of-function mutations in the CF transmembrane conductance regulator (CFTR) protein, a cAMP-regulated anion channel expressed primarily at the apical plasma membrane of secretory epithelia. Nearly 2000 mutations in the CFTR gene have been identified that cause disease by impairing its translation, cellular processing, and/or chloride channel gating. The fundamental premise of CFTR corrector and potentiator therapy for CF is that addressing the underlying defects in the cellular processing and chloride channel function of CF-causing mutant CFTR alleles will result in clinical benefit by addressing the basic defect underlying CF. Correctors are principally targeted at F508del cellular misprocessing, whereas potentiators are intended to restore cAMP-dependent chloride channel activity to mutant CFTRs at the cell surface. This article reviews the discovery of CFTR potentiators and correctors, what is known regarding their mechanistic basis, and encouraging results achieved in clinical testing.
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DOI：
10.1042/bj20110461
发表时间：
2011-04-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Eckford, Paul D W;Bear, Christine E
通讯作者：
Bear, Christine E
影响因子：
3.5
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Kalid, Ori;Mense, Martin;Fischman, Sharon;Shitrit, Alina;Bihler, Hermann;Ben-Zeev, Efrat;Schutz, Nili;Pedemonte, Nicoletta;Thomas, Philip J.;Bridges, Robert J.;Wetmore, Diana R.;Marantz, Yael;Senderowitz, Hanoch
通讯作者：
Senderowitz, Hanoch
影响因子：
56.9
作者：
Egan, ME;Pearson, M;Caplan, MJ
通讯作者：
Caplan, MJ
影响因子：
64.8
作者：
DALEMANS, W;BARBRY, P;LAZDUNSKI, M
通讯作者：
LAZDUNSKI, M
DOI：
10.1165/rcmb.2008-0434oc
发表时间：
2010-03-01
影响因子：
6.4
作者：
Jurkuvenaite, Asta;Chen, Lan;Collawn, James F.
通讯作者：
Collawn, James F.