The NLRP3 inflammasome is a cytosolic multiprotein complex composed of the innate immune receptor protein NLRP3, adapter protein ASC, and inflammatory protease caspase-1 that responds to microbial infection, endogenous danger signals, and environmental stimuli. The assembled NLRP3 inflammasome can activate the protease caspase‐1 to induce gasdermin D-dependent pyroptosis and facilitate the release of IL-1β and IL-18, which contribute to innate immune defense and homeostatic maintenance. However, aberrant activation of the NLRP3 inflammasome is associated with the pathogenesis of various inflammatory diseases, such as diabetes, cancer, and Alzheimer’s disease. Recent studies have revealed that NLRP3 inflammasome activation contributes to not only pyroptosis but also other types of cell death, including apoptosis, necroptosis, and ferroptosis. In addition, various effectors of cell death have been reported to regulate NLRP3 inflammasome activation, suggesting that cell death is closely related to NLRP3 inflammasome activation. In this review, we summarize the inextricable link between NLRP3 inflammasome activation and cell death and discuss potential therapeutics that target cell death effectors in NLRP3 inflammasome-associated diseases.

NLRP3炎症小体是一种胞质多蛋白复合物，由先天免疫受体蛋白NLRP3、接头蛋白ASC和炎症蛋白酶caspase-1组成，对微生物感染、内源性危险信号和环境刺激做出反应。组装的NLRP3炎性体可以激活蛋白酶caspase-1以诱导gasdermin D依赖性焦亡并促进IL-1β和IL-18的释放，这有助于先天免疫防御和稳态维持。然而，NLRP3炎症小体的异常激活与多种炎症疾病的发病机制有关，例如糖尿病、癌症和阿尔茨海默病。最近的研究表明，NLRP3 炎性体激活不仅会导致细胞焦亡，还会导致其他类型的细胞死亡，包括细胞凋亡、坏死性凋亡和铁死亡。此外，据报道，多种细胞死亡效应子可调节NLRP3炎症小体激活，表明细胞死亡与NLRP3炎症小体激活密切相关。在这篇综述中，我们总结了 NLRP3 炎症小体激活与细胞死亡之间不可分割的联系，并讨论了针对 NLRP3 炎症小体相关疾病中细胞死亡效应物的潜在治疗方法。