Diverse functions of NLRP3 inflammasome in PANoptosis and diseases

Abstract NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) is a vital sensor of the innate immune system, capable of responding to various exogenous invading pathogens and endogenous cell injury. Once the danger signal is detected, NLRP3 recruits downstream molecules to assemble into...

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Main Authors: Yuanyuan Jiang, Zhiyuan Qiang, Yue Liu, Liwei Zhu, Long Xiao, Zhenfang Du, Rong Cai, Sheng Qiang
Format: Article
Language:English
Published: Nature Publishing Group 2025-08-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02689-1
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Summary:Abstract NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) is a vital sensor of the innate immune system, capable of responding to various exogenous invading pathogens and endogenous cell injury. Once the danger signal is detected, NLRP3 recruits downstream molecules to assemble into inflammasomes, which induce inflammatory cell death and trigger an inflammatory response. PANoptosis is a specific mode of inflammatory cell death that integrates the processes of pyroptosis, apoptosis, and necrosis. It is primarily driven by a multiprotein complex termed the PANoptosome. The NLRP3 inflammasome, an essential component of the PANoptosome, is implicated in the pathogenesis of several human disorders. Targeted inhibition of NLRP3 activation specifically has a notable impact on mitigating a variety of disease conditions. This review briefly describes how the NLRP3 inflammasome forms and is activated, outlines its multifaceted roles in disorders, and emphasizes the vital role of NLRP3 in PANoptosis. Additionally, we discuss the potential of NLRP3 as a target for the clinical management of associated diseases. Improved understanding of the NLRP3 inflammasome and its involvement in PANoptosis is crucial for guiding new treatment strategies.
ISSN:2058-7716