The NLRP3 Inflammasome as a Target for Antiinflammatory Drugs

Abstract

The Nod-like receptor protein 3 (NLRP3) inflammasome plays a vital role in the nonspecific immune response to inflammatory triggers such as cellular infections, injury, or stressors, and it has also been associated with several inflammation-related diseases. NLRP3 inflammasome activation results in the production of proinflammatory cytokines, contributing to an increased risk of inflammatory conditions, such as cardiovascular, metabolic, infectious, and neurodegenerative diseases. Several signaling pathways and cellular events involved in the NLRP3 inflammasome assembly and activation have been studied, and inhibitory mechanisms have been identified. NLRP3 inflammasome inhibition decreases inflammation and inflammasome-mediated cell death. In prospecting for novel anti-inflammatory therapeutics, signaling molecules upstream or downstream on the NLRP3 inflammasome pathway can serve as viable drug targets. Effective inhibition of these molecules culminates in the downregulation of the expression of proinflammatory cytokines like interleukin-1beta (IL-1β) and IL-18. This chapter elucidates the various classes of NLRP3 inflammasome inhibitors, their resultant anti-inflammatory effects, and various mechanisms of action.