Lihuili Hospital Affiliated to Ningbo University, Ningbo, 315100, Zhejiang, China.
The Eye Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Eur J Pharmacol. 2023 Oct 5;956:175995. doi: 10.1016/j.ejphar.2023.175995. Epub 2023 Aug 11.
Nucleotide-binding leucine-rich repeat-containing receptor 12 (NLRP12), a highly conserved protein containing an N-terminal pyrin domain (PYD), a nucleotide-binding domain and a C-terminal leucine-rich repeat region, belongs to the nucleotide-binding oligomerization domain-like receptor-containing PYD (NLRP) family and is a cytoplasmic sensor that plays a negative role in inflammation. NLRP12 is involved in multiple disease processes, including formation of inflammasomes and regulation of both canonical and noncanonical inflammatory signaling pathways. NLRP12 and pathogenic infections are closely linked, and alterations in NLRP12 expression and activity are associated with inflammatory diseases. In this review, we begin with a summary of the mechanisms of negative regulation by NLRP12. We then underscore the important roles of NLRP12 in the onset and progression of inflammation, infectious disease, host defense, carcinogenesis and COVID-19. Finally, we highlight factors that influence NLRP12 activity, including synthetic and naturally derived agonists, and are regarded as potential therapeutic agents to overcome inflammatory diseases.
核苷酸结合寡聚化结构域样受体蛋白 12（NLRP12），是一种高度保守的蛋白，包含一个 N 端吡咯样受体结构域（PYD）、一个核苷酸结合结构域和一个 C 端亮氨酸富含重复区，属于核苷酸结合寡聚化结构域样受体含有吡咯样受体（NLRP）家族，是一种细胞质传感器，在炎症中发挥负调控作用。NLRP12 参与多种疾病过程，包括炎性小体的形成以及经典和非经典炎症信号通路的调节。NLRP12 与致病性感染密切相关，NLRP12 的表达和活性改变与炎症性疾病有关。在这篇综述中，我们首先总结了 NLRP12 负调控的机制。然后，我们强调了 NLRP12 在炎症、感染性疾病、宿主防御、致癌作用和 COVID-19 发生和进展中的重要作用。最后，我们强调了影响 NLRP12 活性的因素，包括合成和天然衍生的激动剂，这些因素被认为是克服炎症性疾病的潜在治疗药物。
