Enhanced Gasdermin-E-mediated Pyroptosis in Alzheimer's Disease

Qunxian Wang; Shipeng Guo; Dongjie Hu; Xiangjun Dong; Zijun Meng; Yanshuang Jiang; Zijuan Feng; Weihui Zhou; Weihong Song

doi:10.1016/j.neuroscience.2023.11.004

Enhanced Gasdermin-E-mediated Pyroptosis in Alzheimer's Disease

Neuroscience. 2024 Jan 9:536:1-11. doi: 10.1016/j.neuroscience.2023.11.004. Epub 2023 Nov 8.

Authors

Qunxian Wang¹, Shipeng Guo¹, Dongjie Hu¹, Xiangjun Dong¹, Zijun Meng¹, Yanshuang Jiang¹, Zijuan Feng¹, Weihui Zhou², Weihong Song³

Affiliations

¹ Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
² Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. Electronic address: zwh@hospital.cqmu.edu.cn.
³ Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325001, China. Electronic address: weihong@wmu.edu.cn.

PMID: 37944579
DOI: 10.1016/j.neuroscience.2023.11.004

Abstract

Amyloid β protein (Aβ) is a critical factor in the pathogenesis of Alzheimer's disease (AD). Aβ induces apoptosis, and gasdermin-E (GSDME) expression can switch apoptosis to pyroptosis. In this study, we demonstrated that GSDME was highly expressed in the hippocampus of APP23/PS45 mouse models compared to that in age-matched wild-type mice. Aβ treatment induced pyroptosis by active caspase-3/GSDME in SH-SY5Y cells. Furthermore, the knockdown of GSDME improved the cognitive impairments of APP23/PS45 mice by alleviating inflammatory response. Our findings reveal that GSDME, as a modulator of Aβ and pyroptosis, plays a potential role in Alzheimer's disease pathogenesis and shows that GSDME is a therapeutic target for AD.

Keywords: Alzheimer’s disease (AD); Aβ; GSDME; cognitive impairments; pyroptosis.

MeSH terms

Alzheimer Disease*
Amyloid beta-Peptides / metabolism
Animals
Caspase 3 / metabolism
Gasdermins
Humans
Mice
Neuroblastoma*
Pyroptosis / physiology

Substances

Gasdermins
Amyloid beta-Peptides
Caspase 3