Targeting Proteases in Cystic Fibrosis Lung Disease: Paradigms, Progress, and Potential.

Targeting Proteases in Cystic Fibrosis Lung Disease: Paradigms, Progress, and Potential. Am J Respir Crit Care Med. 2019 Oct 18;: Authors: McKelvey MC, Weldon S, McAuley DF, Mall MA, Taggart CC Abstract Cystic fibrosis (CF) is the most common life-limiting hereditary condition of Caucasian populations and is characterised by chronic airways inflammation driving progressive structural lung damage. Despite tremendous advances in the treatment of CF and concomitant increased life expectancy for patients, chronic lung disease remains the main cause of morbidity and mortality among CF patients. While universal restoration of cystic fibrosis transmembrane conductance regulator activity remains a future hope, novel therapies aimed at reducing or preventing chronic airways inflammation and progressive structural lung damage are required. It is well-established that proteolytic enzymes are important in the CF lung beyond the basic turnover of proteins and intracellular degradation of pathogens. When secreted, these enzymes play key roles in extracellular substrate modification implicated in important biological processes such as matrix and airway remodelling, goblet cell metaplasia and mucus hypersecretion, immune cell recruitment and dysregulation of epithelial ion channels. Importantly, the burden of proteases in the CF lung is significantly elevated, overwhelming the endogenous antiprotease shield. Indeed, free protease activity has emerge...
Source: American Journal of Respiratory and Critical Care Medicine - Category: Respiratory Medicine Authors: Tags: Am J Respir Crit Care Med Source Type: research