Correctors of the basic trafficking defect of the mutant F508del-CFTR that causes cystic fibrosis

Abstract

Cystic fibrosis (CF) is the most frequent lethal genetic disease and the most frequent mutation is F508del-cystic fibrosis transmembrane regulator (CFTR). In common with some other protein trafficking diseases the mutant protein is functional but recognized by the cellular quality control system retained in the endoplasmic reticulum (ER) and degraded. There have been some recent impressive advances in developing corrector compounds that restore the trafficking of the mutant protein to the plasma membrane. The targets of these correctors and possible mechanisms of action are discussed.