Hu Bo, Zhang Jiaping, Huang Jie, Luo Bairu, Zeng Xiansi, Jia Jinjing
Department of Pathology and Municipal Key-Innovative Discipline of Molecular Diagnostics, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, Zhejiang Province, China.
Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, Zhejiang Province, China.
Neural Regen Res. 2024 Nov 1;19(11):2400-2410. doi: 10.4103/1673-5374.391311. Epub 2023 Dec 21.
The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis, which is a lytic, inflammatory form of cell death. There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3 (NLRP3) inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer's disease. In this review, we summarize the possible pathogenic mechanisms of Alzheimer's disease, focusing on neuroinflammation. We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer's disease. Finally, we examine the neuroprotective activity of small-molecule inhibitors, endogenous inhibitor proteins, microRNAs, and natural bioactive molecules that target NLRP3 and NLRP1, based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer's disease.
炎性小体是一种参与固有免疫的多蛋白复合物，介导导致细胞焦亡的炎症反应，细胞焦亡是一种溶解性、炎症性细胞死亡形式。越来越多的证据表明，大脑中含核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎性小体介导的小胶质细胞焦亡和含核苷酸结合寡聚化结构域样受体蛋白1（NLRP1）炎性小体介导的神经元焦亡与阿尔茨海默病的发病机制密切相关。在本综述中，我们总结了阿尔茨海默病可能的致病机制，重点关注神经炎症。我们还描述了NLRP3和NLRP1的结构及其激活在阿尔茨海默病中的作用。最后，基于抑制NLRP3和NLRP1炎性小体介导的细胞焦亡可能是治疗阿尔茨海默病的有效策略这一原理，我们研究了靶向NLRP3和NLRP1的小分子抑制剂、内源性抑制蛋白、微小RNA和天然生物活性分子的神经保护活性。
