Dai Yali, Zhou Jing, Shi Chunmeng
Institute of Rocket Force Medicine State Key Laboratory of Trauma and Chemical Poisoning Army Medical University Chongqing China.
Institute of Immunology Army Medical University Chongqing China.
MedComm (2020). 2023 Oct 9;4(5):e391. doi: 10.1002/mco2.391. eCollection 2023 Oct.
Inflammasomes are a group of protein complex located in cytoplasm and assemble in response to a wide variety of pathogen-associated molecule patterns, damage-associated molecule patterns, and cellular stress. Generally, the activation of inflammasomes will lead to maturation of proinflammatory cytokines and pyroptotic cell death, both associated with inflammatory cascade amplification. A sensor protein, an adaptor, and a procaspase protein interact through their functional domains and compose one subunit of inflammasome complex. Under physiological conditions, inflammasome functions against pathogen infection and endogenous dangers including mtROS, mtDNA, and so on, while dysregulation of its activation can lead to unwanted results. In recent years, advances have been made to clarify the mechanisms of inflammasome activation, the structural details of them and their functions (negative/positive) in multiple disease models in both animal models and human. The wide range of the stimuli makes the function of inflammasome diverse and complex. Here, we review the structure, biological functions, and therapeutic targets of inflammasomes, while highlight NLRP3, NLRC4, and AIM2 inflammasomes, which are the most well studied. In conclusion, this review focuses on the activation process, biological functions, and structure of the most well-studied inflammasomes, summarizing and predicting approaches for disease treatment and prevention with inflammasome as a target. We aim to provide fresh insight into new solutions to the challenges in this field.
炎性小体是一组位于细胞质中的蛋白质复合物，可响应多种病原体相关分子模式、损伤相关分子模式和细胞应激而组装。一般来说，炎性小体的激活会导致促炎细胞因子成熟和细胞焦亡，二者均与炎症级联放大有关。一种传感蛋白、一种接头蛋白和一种半胱天冬酶原蛋白通过其功能域相互作用，构成炎性小体复合物的一个亚基。在生理条件下，炎性小体发挥作用以抵抗病原体感染和包括线粒体活性氧、线粒体DNA等在内的内源性危险，而其激活的失调会导致不良后果。近年来，在阐明炎性小体激活机制、其结构细节及其在动物模型和人类多种疾病模型中的功能（负性/正性）方面取得了进展。广泛的刺激使得炎性小体的功能多样且复杂。在此，我们综述炎性小体的结构、生物学功能和治疗靶点，同时重点介绍研究最为深入的NLRP3、NLRC4和AIM2炎性小体。总之，本综述聚焦于研究最为深入的炎性小体的激活过程、生物学功能和结构，总结并预测以炎性小体为靶点的疾病治疗和预防方法。我们旨在为该领域挑战的新解决方案提供新见解。
