β-粉样蛋白的翻译后修饰调节其对细胞机械特性的影响,并影响细胞骨信号级联
Kseniya B Varshavskaya1, Evgeny P Barykin1, Roman V Timoshenko2
1Engelhardt Institute of Molecular Biology, Moscow, Russia.
Frontiers in molecular neuroscience
|November 29, 2024
概括
贝塔-粉样蛋白 (Aβ) 的翻译后修饰会影响阿尔茨海默病 (AD) 的发病. 不同的Aβ异型通过不同的信号通路改变神经元细胞机制和活性氧物种 (ROS) 水平.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生物化学
- 细胞生物学 细胞生物学
背景情况:
- β-粉样蛋白 (Aβ) 的翻译后修饰 (PTM) 与阿尔茨海默病 (AD) 病原发生有关.
- 像化Ser8 (pS8-Aβ42) 和异构化Asp7 (iso-Aβ42) 等Aβ异型体,表现出改变的特性和体内存在.
- Aβ异型的异性致病性可能源于不同的信号级联影响细胞机械性质.
研究的目的:
- 研究不同Aβ异型对神经元细胞机械性质 (Young的模量) 和反应性氧物种 (ROS) 水平的影响.
- 为了比较未经修改的Aβ42,ps8-Aβ42和iso-Aβ42对SH-SY5Y细胞的影响.
- 通过各种Aβ异型来分析参与actin细胞骨调节的信号蛋白的调节.
主要方法:
- 使用相对扫描离子导电显微镜 (SICM) 来测量细胞模量.
- 使用pt-纳米电极来评估活性氧物种 (ROS) 水平.
- 进行了西斑分析,以检查信号蛋白的水平 (cofilin,GSK3β,LIMK,ERK,p38).
主要成果:
- 未经修改的Aβ42在4小时后显著增加了细胞Young的模量.
- 在24小时后,pS8-Aβ42诱导了细胞硬度和ROS水平的最显著增加.
- 不同的Aβ异型不同影响了cofilin,GSK3β,LIMK,ERK和p38信号通路.
结论:
- Aβ的PTMs调节其与神经元细胞的相互作用.
- 亚β异型会触发不同的信号级联,导致细胞机械性质的改变和ROS的产生.
- 这些发现突显了Aβ修饰在AD病变发生过程中通过机械转导途径发挥的作用.
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