The mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors

Xiaoyan Zhan; Qiang Li; Guang Xu; Xiaohe Xiao; Zhaofang Bai

doi:10.3389/fimmu.2022.1109938

The mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors

Front Immunol. 2023 Jan 18:13:1109938. doi: 10.3389/fimmu.2022.1109938. eCollection 2022.

Authors

Xiaoyan Zhan^{1

2}, Qiang Li^{1

2}, Guang Xu^{1

2}, Xiaohe Xiao^{1

2}, Zhaofang Bai^{1

2}

Affiliations

¹ Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
² China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

Abstract

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 cryopyrin-associated 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.

Keywords: NLRP3; inflammasome; inflammatory diseases; pattern recognition receptor; pharmacological inhibitors.

Publication types

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

MeSH terms

Caspase 1 / metabolism
Cryopyrin-Associated Periodic Syndromes*
Diabetes Mellitus, Type 2*
Humans
Inflammasomes / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism

Substances

Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
Caspase 1

Grants and funding

This review was supported by National Natural Science Foundation of China (Grant No. 81630100, 81930110, 81874368, 82003984, 81721002), Beijing Natural Science Foundation (Grant No. 7214296), National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program” (Grant No. 2017ZX09301022), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (Grant No. ZYYCXTD-C-202005).