Attempts to promote normal processing and function of F508del-CFTR, the most common mutant in cystic fibrosis (CF), have been described as potential therapeutic strategies in the management of this disease. Here we described the proteomic approaches, namely two-dimensional electrophoresis (2DE), mass spectrometry (MS), and bioinformatics tools used in our recent studies to gain insight into the...

BACKGROUND Ivacaftor improves clinical outcome by potentiation of mutant G551D CFTR. Due to the presence of CFTR in monocytes and polymorphonuclear neutrophils (PMNs), we hypothesized that ivacaftor may impact leukocyte activation. METHODS We examined blood leukocytes from G551D CF subjects prior to and at one and six months after receiving ivacaftor. Blood leukocytes from ivacaftor-naïve G55...

A depressed autophagy has previously been reported in cystic fibrosis patients with the common F508del-CFTR mutation. This report describes the synthesis and preliminary biological characterization of a novel series of autophagy activators involving fatty acid cysteamine conjugates. These molecular entities were synthesized by first covalently linking cysteamine to docosahexaenoic acid. The res...

Background Cystic fibrosis (CF) is a major life-limiting genetic disease leading to severe respiratory symptoms caused by mutations in CF trans membrane conductance regulator (CFTR), a chloride channel expressed at the apical membrane of epithelial cells. Absence of functional CFTR from the surface of respiratory cells reduces mucociliary clearance, promoting airways obstruction, chronic infect...

The past two decades have seen most research efforts targeted at correcting the ion transport deficiency of cystic fibrosis (CF), highlighting the required promotion and development of new drugs to tackle CF (Becq et al., 2011; Boyle and De Boeck, 2013; Riordan, 2008). The polyexocrinopathy genetic disease CF is caused by one of the 2000 documented mutations in the cystic fibrosis transmembrane...

The function of cystic fibrosis transmembrane conductance regulator (CFTR) channels is crucial in human airways. However unfortunately, chronic Pseudomonas aeruginosa infection has been shown to impair CFTR proteins in non-CF airway epithelial cells (AEC) and to alter the efficiency of new treatments with CFTR modulators designed to correct the basic CFTR default in AEC from cystic fibrosis (CF...

The cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is essential to maintain fluid homeostasis in key organs. Functional impairment of CFTR due mutations the cftr gene leads fibrosis. Here, we show that first nucleotide-binding domain (NBD1) can spontaneously adopt an alternate conformation departs from canonical NBD fold previously observed. Crystallography reveals thi...

The cystic fibrosis transmembrane regulator (CFTR) is a cyclic-AMP dependent chloride channel expressed at the apical surface of epithelial cells lining various organs such as the respiratory tract. Defective processing and functioning of this protein caused by mutations in the CFTR gene results in loss of ionic balance, defective mucus clearance, increased proliferation of biofilms and inflamm...

INTRODUCTION Cystic fibrosis (CF) is one of the common genetic disorders in the western world. It has been reported to be very rare in Asian populations. According to the Cystic Fibrosis Genetic Analysis Consortium, more than 1,000 mutations of the CF gene have been identified. The CF gene, named the cystic fibrosis transmembrane conductance regulator (CFTR), is located on chromosome 7 and comp...