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Neuroscience

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

Published:8 November 2023 DOI: PMID: 37944579
Qunxian Wang , Shipeng Guo , Dongjie Hu , Xiangjun Dong , Zijun Meng , Yanshuang Jiang , Zijuan Feng , Weihui Zhou , Weihong Song

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.

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