The nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome is a high-molecular-weight complex mediated by the activation of pattern-recognition receptors (PRRs) seed in innate immunity. Once NLRP3 is activated, the following recruitment of the adapter apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD) (ASC) and procaspase-1 would be initiated. Cleavage of procaspase-1 into active caspase-1 then leads to the maturation of the precursor forms of interleukin (IL)-1β and IL-18 into biologically active IL-1β and IL-18. The activation of NLRP3 inflammasome is thought to be tightly associated with a regulator never in mitosis A (NIMA)-related kinase 7 (NEK7), apart from other signaling events such as K⁺ efflux and reactive oxygen species (ROS). Plus, the NLRP3 inflammasome has been linked to various metabolic disorders, chronic inflammation and other diseases. In this review, we firstly describe the cellular/molecular mechanisms of the NEK7-licensed NLRP3 inflammasome activation. Then we detail the potential inhibitors that can selectively and effectively modulate either the NEK7-NLRP3 complex itself or the related molecular/cellular events. Finally, we describe some inhibitors as promising therapeutic strategies for diverse diseases driven by NLRP3 inflammasome.

包含 pyrin 结构域 3 (NLRP3) 炎性体的核苷酸结合寡聚化结构域 (NOD) 样受体是一种高分子量复合物，由先天免疫中模式识别受体 (PRR) 种子的激活介导。一旦 NLRP3 被激活，将启动包含半胱天冬酶募集结构域 (CARD) (ASC) 和 procaspase-1 的适配器凋亡相关斑点样蛋白的后续募集。procaspase-1 裂解为活性 caspase-1，然后导致白细胞介素 (IL)-1β 和 IL-18 的前体形式成熟为具有生物活性的 IL-1β 和 IL-18。NLRP3 炎症小体的激活被认为与从未参与有丝分裂 A (NIMA) 相关激酶 7 (NEK7) 的调节剂密切相关，除了其他信号事件，如 K ⁺外排和活性氧 (ROS)。此外，NLRP3 炎症小体与各种代谢紊乱、慢性炎症和其他疾病有关。在这篇综述中，我们首先描述了 NEK7 许可的 NLRP3 炎症小体激活的细胞/分子机制。然后我们详细介绍了可以选择性和有效地调节 NEK7-NLRP3 复合物本身或相关分子/细胞事件的潜在抑制剂。最后，我们将一些抑制剂描述为针对 NLRP3 炎症小体驱动的多种疾病的有希望的治疗策略。