An overview of disease models for NLRP3 inflammasome over-activation

Introduction: Inflammatory reactions, including those mediated by the NLRP3 inflammasome, maintain the body's homeostasis by removing pathogens, repairing damaged tissues, and adapting to stressed environments. However, uncontrolled activation of the NLRP3 inflammasome tends to cause various diseases using different mechanisms. Recently, many inhibitors of the NLRP3 inflammasome have been reported and many are being developed. In order to assess their efficacy, specificity, and mechanism of action, the screening process of inhibitors requires various types of cell and animal models of NLRP3-associated diseases.Areas covered: In the following review, the authors give an overview of the cell and animal models that have been used during the research and development of various inhibitors of the NLRP3 inflammasome.Expert opinion: There are many NLRP3 inflammasome inhibitors, but most of the inhibitors have poor specificity and often influence other inflammatory pathways. The potential risk for cross-reaction is high; therefore, the development of highly specific inhibitors is essential. The selection of appropriate cell and animal models, and combined use of different models for the evaluation of these inhibitors can help to clarify the target specificity and therapeutic effects, which is beneficial for the development and application of drugs targeting the NLRP3 inflammasome.

引言：炎症反应，包括由NLRP3炎症小体介导的炎症反应，通过清除病原体、修复受损组织以及适应应激环境来维持机体的内稳态。然而，NLRP3炎症小体不受控制的激活往往会通过不同机制引发多种疾病。近期，已有许多NLRP3炎症小体抑制剂被报道，并且还有很多正在研发中。为了评估它们的功效、特异性和作用机制，抑制剂的筛选过程需要多种NLRP3相关疾病的细胞和动物模型。 涵盖领域：在接下来的综述中，作者概述了在各种NLRP3炎症小体抑制剂研发过程中所使用的细胞和动物模型。 专家观点：NLRP3炎症小体抑制剂众多，但大多数抑制剂特异性较差，常常影响其他炎症通路。交叉反应的潜在风险较高；因此，开发高特异性的抑制剂至关重要。选择合适的细胞和动物模型，并联合使用不同模型来评估这些抑制剂，有助于明确靶点特异性和治疗效果，这对开发和应用针对NLRP3炎症小体的药物是有益的。