Pathophysiological roles of proteases in gastrointestinal disease

Gastrointestinal diseases, such as irritable bowel syndrome, inflammatory bowel disease, and colorectal cancer, affect a large proportion of the population and are associated with many unpleasant symptoms. Although the causes of these diseases remain largely unknown, there is increasing evidence to suggest that dysregulated protease activity may be a contributing factor. Proteases are enzymes that cleave other proteins, and their activity is normally very tightly regulated. During disease, however, the balance between proteases and their inhibitors is often shifted, leading to altered spatial and temporal control of substrate cleavage. Evaluating protease levels in normal physiology and disease has relied heavily on the use of chemical tools. Although these tools have greatly advanced the field, they are not without caveats. This review provides an introduction to these tools, their application in the gut, and a summary of the current knowledge on the contribution of protease activity to gastrointestinal disease.