在阿尔茨海默病的小鼠模型中展开的蛋白质反应:寻找预测因素
Giulia Sita1, Agnese Graziosi1, Camilla Corrieri1
1Department of Pharmacy and BioTechnology-FaBiT, Alma Mater Studiorum University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
International journal of molecular sciences
|November 25, 2023
概括
阿尔茨海默氏症涉及到内质网膜压力和未折叠蛋白质反应 (UPR) 激活. 准UPR通路可能为AD提供新的神经保护策略.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 病理学 病理学 病理学
背景情况:
- 阿尔茨海默病 (AD) 是导致痴呆的主要原因,衰老是主要的危险因素.
- 细胞内膜网膜 (ER) 功能障碍,以粉样蛋白-β (Aβ) 和陶蛋白积累为标志,与AD病变发生有关.
- 展开的蛋白质反应 (UPR) 是一种恢复ER平衡的细胞机制.
研究的目的:
- 在由Aβ寡合体诱导的AD小鼠模型中研究UPR的作用.
- 分析ER应激对老鼠神经退行性路径的影响.
主要方法:
- 内脑内脑 (ICV) 的情况. 在3个月和18个月大的小鼠中注射Aβ小分子.
- 评估记忆障碍,氧化应激和谷氨水平.
- RNA测序和生物信息分析以确定失调的途径.
主要成果:
- 在老年小鼠中注射Aβ会导致记忆力缺陷,氧化应激和缺乏谷氨.
- RNA测序揭示了神经退行和蛋白质调节通路的丰富.
- 观察到PERK,IRE1α和ATF-6 (关键UPR组件) 的显著调节失调.
- ER压力影响PI3K/Akt/Gsk3β和MAPK/ERK信号通路.
结论:
- 在Aβ诱导的AD小鼠模型中,UPR显著改变.
- Mapkapk5成为阿尔茨海默病的潜在标志物.
- 调节UPR和相关途径可能为阿尔茨海默病带来新的治疗策略.
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