Cystic fibrosis

The Distribution and Role of the CFTR Protein in the Intracellular Compartments

“…Today, small molecule drugs (SMDs) already approved by the FDA can bring clinical benefits to approximately 90% of CF patients carrying the most common mutations (i.e., F508del) on at least one allele gating and conductance mutations. Novel treatment strategies target the CFTR at various levels, which include increasing CFTR mRNA levels (nonsense-mediated mRNA decay (NMD) inhibitors); suppressing translation termination at premature stop codon (PTC) in CFTR mRNA (readthrough therapies); correction of CFTR folding and trafficking to apical membrane (correctors); increasing the channel function (potentiators); stimulation of CFTR expression (amplifiers); and increasing the stability/decreasing degradation rate of CFTR protein at the plasma membrane (stabilizers) [177,178]. Some of the best known SMDs are CFTR corrector VX-809 (lumacaftor) for class II mutations and CFTR potentiator VX-770 (ivacaftor) for the G551D mutation [179].…”

Editorial: Novel Anti-Inflammatory Approaches for Cystic Fibrosis Lung Disease: Identification of Molecular Targets and Design of Innovative Therapies

“…Novel Anti-Inflammatory Approaches for Cystic Fibrosis Lung Disease: Identification of Molecular Targets and Design of Innovative Therapies Cystic Fibrosis (CF) is a monogenic disease caused by mutations of the Cystic Fibrosis (CF) Transmembrane conductance Regulator (CFTR) gene encoding a chloride and bicarbonate transporter (Kerem et al, 1989;Riordan et al, 1989;Rommens et al, 1989). CF disease affects different organs, with the chronic lung pathology being the main cause of morbidity and reduction of life expectancy of these patients (Shteinberg et al, 2021). Pulmonary disease has been demonstrated since early infancy and progresses with airways obstruction and bronchial damages, representing the major challenge for the cure of these patients (Stoltz et al, 2015).…”

Bacterial Subversion of Autophagy in Cystic Fibrosis

“…Cystic fibrosis (CF) is an autosomal recessive congenital disease (O'Sullivan and Freedman, 2009;Shteinberg et al, 2021) that principally affects lungs, pancreas, liver, kidneys, and intestine of at least 70,000 people worldwide (Jackson and Goss, 2018). The condition is due to a mutation in the cftr gene (Tsui et al, 1985), that codes a CF transmembrane conductance regulator (CFTR) involved in the transport of chloride and sodium ions, HCO − 3 , and water across the lung epithelia (Shteinberg et al, 2021).…”

“…Cystic fibrosis (CF) is an autosomal recessive congenital disease (O'Sullivan and Freedman, 2009;Shteinberg et al, 2021) that principally affects lungs, pancreas, liver, kidneys, and intestine of at least 70,000 people worldwide (Jackson and Goss, 2018). The condition is due to a mutation in the cftr gene (Tsui et al, 1985), that codes a CF transmembrane conductance regulator (CFTR) involved in the transport of chloride and sodium ions, HCO − 3 , and water across the lung epithelia (Shteinberg et al, 2021). Defective CFTR function produces a thick and sticky mucus (Boyle, 2007) that rapidly clogs the lower airways in which diverse bacterial pathogens might produce infection and inflammation that gradually decrease the lung function (Blanchard and Waters, 2019), leading to the production of thick sticky mucus.…”