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.


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


  • Gasdermins
  • Amyloid beta-Peptides
  • Caspase 3