Protease inhibition as new therapeutic strategy for GI diseases

Gut. 2016 Jul;65(7):1215-24. doi: 10.1136/gutjnl-2015-309147. Epub 2016 Apr 12.

Abstract

The GI tract is the most exposed organ to proteases, both in physiological and pathophysiological conditions. For digestive purposes, the lumen of the upper GI tract contains large amounts of pancreatic proteases, but studies have also demonstrated increased proteolytic activity into mucosal tissues (both in the upper and lower GI tract), associated with pathological conditions. This review aims at outlining the evidences for dysregulated proteolytic homeostasis in GI diseases and the pathogenic mechanisms of increased proteolytic activity. The therapeutic potential of protease inhibition in GI diseases is discussed, with a particular focus on IBDs, functional GI disorders and colorectal cancer.

Keywords: ENZYMOLOGY; INFLAMMATORY BOWEL DISEASE; INFLAMMATORY BOWEL SYNDROME; INFLAMMATORY MECHANISMS.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Celiac Disease / drug therapy
  • Colorectal Neoplasms / drug therapy
  • Gastrointestinal Diseases / drug therapy*
  • Gastrointestinal Diseases / enzymology*
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Peptide Hydrolases / physiology*
  • Protease Inhibitors / therapeutic use*

Substances

  • Protease Inhibitors
  • Peptide Hydrolases