NLRP3 inhibitors: Unleashing their therapeutic potential against inflammatory diseases

Biochem Pharmacol. 2023 Dec:218:115915. doi: 10.1016/j.bcp.2023.115915. Epub 2023 Nov 8.

Abstract

The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome has been linked to the release of pro-inflammatory cytokines and is essential for innate defence against infection and danger signals. These secreted cytokines improve the inflammatory response caused by tissue damage and associated inflammation. Consequently, the development of NLRP3 inflammasome inhibitors are viable option for the treatment of diverse inflammatory disorders. The significant anti-inflammatory effects of the NLRP3 inhibitors have severe side effects. Hence, the application of NLRP3 inhibitors against inflammatory disease has not yet been understood and most of the developed inhibitors are unsuccessful in clinical trials. The processes behind the NLRP3 complex, priming, and activation are the main emphasis of this review, which also covers therapeutical inhibitors of the NLRP3 inflammasome and potential therapeutic strategies for directing the NLRP3 inflammasome towards clinical development.

Keywords: Clinical development; Molecular targets; NLRP3 inflammasome; Natural products; Synthetic drugs.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines
  • Humans
  • Inflammasomes* / metabolism
  • Inflammation / drug therapy
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Cytokines