中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (on line): 1-8.

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

  

  • 出版日期:2024-01-01 发布日期:2023-11-14

Bo Hu1, Jiaping Zhang2, Jie Huang2, Bairu Luo3, Xiansi Zeng2, Jinjing Jia2,*   

  1. 1Department of Pathology and Municipal Key-Innovative Discipline of Molecular Diagnostics, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, Zhejiang Province, China; 2Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, Zhejiang Province, China; 3Department of Clinical Pathology, Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Jiaxing, Zhejiang Province, China
  • Online:2024-01-01 Published:2023-11-14
  • Contact: Jinjing Jia, PhD, jiajinjing1986@126.com.
  • Supported by:
    This work was supported by the Natural Science Foundation of Zhejiang Province of China, Nos. LQ22H090003 (to JJ), LTGY23C090001 (to XZ), LY23H020008 (to BH) and Sci-Tech Planning Project of Jiaxing, Nos. 2021AY30001 (to XZ) and 2022AY30020 (to JJ).

摘要: https://orcid.org/0000-0002-0034-3199 (Jinjing Jia)

Abstract: 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 disease (AD). In this review, we summarize the possible pathogenic mechanisms of AD, focusing on neuroinflammation. We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in AD. 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 AD.

Key words: Alzheimer disease, caspase-1, GSDMD, inflammasome, neuroinflammation, NLRP1, NLRP3, pyroptosis, therapeutic strategies