在阿尔茨海默病中通过准综合应激反应来恢复葡萄糖代谢
Hui Sun1, Shenrui Guo1, Hongfu Jin1
1Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
概括
针对综合应激反应 (ISR) 途径可能为阿尔茨海默病 (AD) 提供新的治疗策略. 在AD小鼠模型中,抑制ISR激活恢复了葡萄糖代谢并改善了认知功能.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生物化学
- 病理学 病理学 病理学
背景情况:
- 阿尔茨海默病 (AD) 与大脑葡萄糖代谢减少有关.
- 目前的阿尔茨海默病疗法侧重于粉样β (Aβ) 和病理.
- 恢复大脑葡萄糖代谢是一种潜在的治疗途径.
研究的目的:
- 研究AD中葡萄糖低代谢和神经元死亡之间的联系.
- 确定AD中降低葡萄糖载体表达的基础分子机制.
- 评估针对AD的综合应激反应 (ISR) 途径的治疗潜力.
主要方法:
- 使用了三重转基因AD (3xTg-AD) 的小鼠模型.
- 评估葡萄糖代谢,神经元死亡和葡萄糖载体 (GLUT1/3) 表达.
- 检查了综合应激反应 (ISR) 路径激活.
- 在体外和体内给予ISR抑制剂ISRIB.
主要成果:
- 在3xTg-AD小鼠中,葡萄糖低代谢先于神经元死亡.
- 观察到GLUT1和GLUT3的表达减少,与ISR激活有关.
- Aβ和Tau酸化有助于ISR激活,并降低了GLUT1/3的表达.
- 在3xTg-AD小鼠中,ISRIB治疗恢复了GLUT1/3的表达,改善了认知功能和葡萄糖代谢.
结论:
- 异常的ISR激活有助于AD中的葡萄糖代谢受损.
- 准ISR途径以恢复葡萄糖载体表达是一种有前途的AD治疗策略.
- 通过改善大脑葡萄糖代谢和认知能力,ISRIB显示出治疗AD的潜力.
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