Inflammation drives many devastating human diseases for which patients have no disease-modifying drugs. Indeed, inflammation contributes to the susceptibility or severity of all top 10 causes of human deaths; accounting for 55% of global deaths. The inflammasome pathway is a key driver of pathological inflammation in this context, contributing to several common human diseases (e.g. metabolic disease, neurodegenerative diseases, cancers).
Inflammasomes are signalling hubs that provide an activation platform for the zymogen protease, caspase-1. Upon activation, caspase-1 triggers the maturation and secretion of potent pro-inflammatory mediators (interleukins (IL)-1b and -18) and induces cell lysis, culminating in immune system activation. Here, we reveal new mechanisms by which inflammasomes signal, and how a small molecule inflammasome inhibitor can silence pathological inflammasome signalling for therapeutic management of several human diseases.