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

p protein (Ap) is a critical factor in the pathogenesis of Alzheimer's disease (AD). Ap 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. Ap 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 Ap and pyroptosis, plays a potential role in Alzheimer's disease pathogenesis and shows that GSDME is a therapeutic target for AD.(c) 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.