Jiang Yuanyuan, Qiang Zhiyuan, Liu Yue, Zhu Liwei, Xiao Long, Du Zhenfang, Cai Rong, Qiang Sheng
Translational Medical Innovation Center, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, China.
School of Medicine Southeast University, Nanjing, Jiangsu, China.
Cell Death Discov. 2025 Aug 19;11(1):389. doi: 10.1038/s41420-025-02689-1.
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.
NOD样受体(NLR)家族含pyrin结构域3(NLRP3)是天然免疫系统的重要传感器,能够对各种外源入侵病原体和内源性细胞损伤作出反应。一旦检测到危险信号,NLRP3就会招募下游分子组装成炎性小体,从而诱导炎性细胞死亡并引发炎症反应。泛凋亡是一种整合了焦亡、凋亡和坏死过程的炎性细胞死亡的特定模式。它主要由一种称为泛凋亡小体的多蛋白复合物驱动。NLRP3炎性小体是泛凋亡小体的重要组成部分,与多种人类疾病的发病机制有关。特异性靶向抑制NLRP3激活对减轻多种疾病状况具有显著影响。本综述简要描述了NLRP3炎性小体如何形成和激活,概述了其在疾病中的多方面作用,并强调了NLRP3在泛凋亡中的重要作用。此外,我们还讨论了NLRP3作为相关疾病临床治疗靶点的潜力。深入了解NLRP3炎性小体及其在泛凋亡中的作用对于指导新的治疗策略至关重要。