The epithelial sodium channel (ENaC) as a therapeutic target for cystic fibrosis lung disease

Expert Opinion on Therapeutic Targets
Patrick J Moore, Robert Tarran

Abstract

Cystic fibrosis is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that codes for the CFTR anion channel. In the absence of functional CFTR, the epithelial Na+ channel is also dysregulated. Airway surface liquid (ASL) hydration is maintained by a balance between epithelial sodium channel (ENaC)-led Na+ absorption and CFTR-dependent anion secretion. This finely tuned homeostatic mechanism is required to maintain sufficient airway hydration to permit the efficient mucus clearance necessary for a sterile lung environment. In CF airways, the lack of CFTR and increased ENaC activity lead to ASL/mucus dehydration that causes mucus obstruction, neutrophilic infiltration, and chronic bacterial infection. Rehydration of ASL/mucus in CF airways can be achieved by inhibiting Na+ absorption with pharmacological inhibitors of ENaC. Areas covered: In this review, we discuss ENaC structure and function and its role in CF lung disease and focus on ENaC inhibition as a potential therapeutic target to rehydrate CF mucus. We also discuss the failure of the first generation of pharmacological inhibitors of ENaC and recent alternate strategies to attenuate ENaC activity in t...Continue Reading

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Feb 15, 2019·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Marianne SkovTacjana Pressler
Jun 7, 2019·Expert Opinion on Therapeutic Targets·John W HanrahanDavid Y Thomas
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