抑制AGE-RAGE-PP2A轴缓解慢性心力衰竭后的认知障碍
Shaodong Li1, Linhai Wang2, Junyan Wang3
1The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. jishaokang19750515@163.com.
Cellular and molecular biology (Noisy-le-Grand, France)
|August 12, 2023
概括
针对AGE-RAGE-PP2A通路有效地减轻慢性心力衰竭小鼠的认知障碍,通过减少大脑粉样β和病理.
科学领域:
- 神经科学是一个神经科学.
- 心脏病学 心脏病学
- 生物化学 生物化学
背景情况:
- 慢性心力衰竭 (CHF) 与认知障碍 (CI) 有关.
- AGEs-RAGE-PP2A信号轴与神经退行过程有关.
研究的目的:
- 研究AGE-RAGE-PP2A轴在CHF引起的认知障碍中的作用.
- 为了评估针对这一轴的治疗潜力.
主要方法:
- 小鼠接受了横向大动脉收缩 (TAC) 诱导CHF.
- 这些组包括Sham,TAC,RAGE缺乏的TAC,用aminoguanidine (AGEs抑制剂) 治疗的TAC和用FTY720 (PP2A激活剂) 治疗的TAC.
- 评估了心脏功能,行为测试,大脑组织学和蛋白质表达 (Aβ,p-tau,亡标志物,PP2A).
主要成果:
- 氨基瓜尼丁和RAGE缺乏在TAC小鼠中显著改善了心脏和认知功能.
- FTY720部分改善了心脏功能,但显著改善了认知功能.
- 所有干预措施都降低了大脑Aβ和p-tau,调节了与亡相关的蛋白质,并上调了PP2A表达.
结论:
- 缺少AGE或RAGE和PP2A激活,可以减轻CHF小鼠的认知障碍.
- 这些干预措施通过减少Aβ,p-tau和apoptotic蛋白质表达来保护大脑结构.
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