Inhibition of Serine Proteases as a Novel Therapeutic Strategy for Abdominal Pain in IBS

Abstract

Serine proteases are heavily present in the gastrointestinal tract where they are essential in numerous physiological processes. An imbalance in the proteolytic activity is a central mechanism underlying abdominal pain in irritable bowel syndrome (IBS). Therefore, protease inhibitors are emerging as a promising therapeutic tool to manage abdominal pain in this functional gastrointestinal disorder. With this review, we provide an up-to-date overview of the implications of serine proteases in the development of abdominal pain in IBS, along with a critical assessment of the current developments and prospects of protease inhibitors as a therapeutic tool. In particular, we highlight the current knowledge gap concerning the identity of dysregulated serine proteases that are released by the rectal mucosa of IBS patients. Finally, we suggest a workflow with state-of-the-art techniques that will help address the knowledge gap, guiding future research towards the development of more effective and selective protease inhibitors to manage abdominal pain in IBS.

Keywords: irritable bowel syndrome; protease inhibitors; protease-activated receptors; proteases; visceral hypersensitivity.