增强的 Gasdermin-E 介导热激蛋白细胞死亡在阿尔茨海默病中的作用。

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

机构信息

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.

出版信息

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

DOI:10.1016/j.neuroscience.2023.11.004

PMID:37944579

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.

摘要

淀粉样β蛋白（Aβ）是阿尔茨海默病（AD）发病机制中的关键因素。Aβ诱导细胞凋亡，而gasdermin-E（GSDME）的表达可以将细胞凋亡转换为细胞焦亡。在本研究中，我们发现与年龄匹配的野生型小鼠相比，APP23/PS45 小鼠模型的海马体中 GSDME 表达水平升高。Aβ 处理通过活性 caspase-3/GSDME 在 SH-SY5Y 细胞中诱导细胞焦亡。此外，敲低 GSDME 通过减轻炎症反应改善了 APP23/PS45 小鼠的认知障碍。我们的研究结果表明，GSDME 作为 Aβ和细胞焦亡的调节剂，在阿尔茨海默病发病机制中发挥着潜在作用，并表明 GSDME 是 AD 的治疗靶点。