Frontiers in Immunology (Jan 2023)

The mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors

  • Xiaoyan Zhan,
  • Xiaoyan Zhan,
  • Qiang Li,
  • Qiang Li,
  • Guang Xu,
  • Guang Xu,
  • Xiaohe Xiao,
  • Xiaohe Xiao,
  • Zhaofang Bai,
  • Zhaofang Bai

DOI
https://doi.org/10.3389/fimmu.2022.1109938
Journal volume & issue
Vol. 13

Abstract

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NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is a cytosolic pattern recognition receptor (PRR) that recognizes multiple pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Once activated, NLRP3 initiates the inflammasome assembly together with the adaptor ASC and the effector caspase-1, leading to caspase-1 activation and subsequent cleavage of IL-1β and IL-18. Aberrant NLRP3 inflammasome activation is linked with the pathogenesis of multiple inflammatory diseases, such as cryopyrin­associated periodic syndromes, type 2 diabetes, non-alcoholic steatohepatitis, gout, and neurodegenerative diseases. Thus, NLRP3 is an important therapeutic target, and researchers are putting a lot of effort into developing its inhibitors. The review summarizes the latest advances in the mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors.

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