NLRP3/1-mediated pyroptosis:beneficial clues for the development of novel therapies for Alzheimer’s disease  

作　　者：Bo Hu Jiaping Zhang Jie Huang Bairu Luo Xiansi Zeng Jinjing Jia 

机构地区：[1]Department of Pathology and Municipal Key-Innovative Discipline of Molecular Diagnostics,Jiaxing Hospital of Traditional Chinese Medicine,Jiaxing University,Jiaxing,Zhejiang Province,China [2]Research Center of Neuroscience,Jiaxing University Medical College,Jiaxing,Zhejiang Province,China [3]Department of Clinical Pathology,Jiaxing University Master Degree Cultivation Base,Zhejiang Chinese Medical University,Jiaxing,Zhejiang Province,China

出　　处：《Neural Regeneration Research》2024年第11期2400-2410,共11页中国神经再生研究（英文版）

基　　金：supported by the Natural Science Foundation of Zhejiang Province of China,Nos.LQ22H090003(to JJ),LTGY23C090001(to XZ),LY23H020008(to BH);Sci-Tech Planning Project of Jiaxing,Nos.2021AY30001(to XZ)and 2022AY30020(to JJ).

摘　　要：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.

关 键 词：Alzheimer’s disease caspase-1 GSDMD INFLAMMASOME NEUROINFLAMMATION NLRP1 NLRP3 PYROPTOSIS therapeutic strategies 

分 类 号：R749.16[医药卫生—神经病学与精神病学]