NLRP3 Inflammasome: Mechanism of Action, Role, and Therapeutics in Liver Diseases (preprint)

ABSTRACT

Liver inflammation is a universal characteristic of chronic liver diseases. NLRP3 is an intracellular sensor that recognizes various endogenous danger signals and environmental irritants, contributing to the formation and activation of the NLRP3 inflammasome. NLRP3 inflammasome is closely related to the progression of various liver diseases and is strongly associated with replicating COVID-19, which is still spreading globally. The assembly and activation of NLRP3 inflammasome in the liver diseases aggravate inflammation and subsequent fibrosis, and this effect is abolished by genetic or pharmacologic deletion of NLRP3 inflammasome. Here, we summarized the latest advances in the critical regulatory role of NLRP3 inflammasome in a variety of liver diseases, including COVID-19 induced liver diseases, NAFLD, ALD, and ischemia-reperfusion (I/R) injury. Additionally, we also discuss small-molecule inhibitors identifying the NLRP3 inflammasome signaling are novel therapeutic targets in treating liver diseases. Our review provides novel insights into the underlying mechanisms of NLRP3 inflammasome in liver diseases and may offer a potential therapeutic strategy for treating liver diseases by targeting NLRP3 inflammasome.