基础科学和病原发生学
Roberto A Guzman-Hernandez1, Silvia Fossati2
1Temple University, Phialdelphia, PA, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 25, 2025
概括
聚陶通过激活RAGE和产生AGE来损害大脑内皮细胞,导致屏障功能障碍. 准这些通路可能会防止神经血管损伤.
科学领域:
- 神经科学是一个神经科学.
- 血管生物学 血管生物学
- 细胞生物学 细胞生物学
背景情况:
- 聚合的陶蛋白可以在整个大脑中传播,可能导致脑血管和神经血管单元功能障碍.
- 影响内皮细胞 (ECs) 的机制尚不清楚,但对于了解神经退行症早期血管变化至关重要.
- 原纤维素会诱导EC的炎症和代谢变化,损害屏障功能.
研究的目的:
- 为了研究先进的糖化终产品 (RAGE) 和先进的糖化终产品 (AGEs) 的受体在tau诱导的EC功能障碍中的作用.
- 为了确定抑制RAGE或AGE的产生是否可以防止tau介导的内皮屏障损伤.
主要方法:
- 人类大脑的微血管EC被暴露在原纤维素中,并用RAGE抑制剂或AGE清除剂进行治疗.
- 使用RAGE淘汰赛EC来评估RAGE的直接作用.
- 测量包括屏障完整性的跨内皮电阻 (TEER),用于炎症的细胞因子生产和EC生物能学.
- 西方涂抹被用于检测VCAM-1,RAGE和tau的蛋白质水平.
主要成果:
- 原纤维素降低了TEER和增加了葡萄糖分解,导致了亲炎性EC表型,这种表型通过代谢调节被逆转.
- 抑制RAGE减少了tau进入ECs,逆转了炎症,并防止了屏障功能障碍和代谢变化.
- 抑制TAU介导的AGE产生也可以防止屏障损失和增加糖解.
- RAGE删除保护了ECs免受屏障和代谢损伤.
结论:
- 纤维状激活RAGE信号,导致EC屏障功能障碍和炎症.
- 介导的AGE产生起到中间作用,维持RAGE激活和代谢变化.
- 这些发现阐明了tau诱导的EC功能障碍的机制,突出了RAGE和AGE作为潜在的治疗点.
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