通过神经元活动从人类ReNCell VM培养物中释放的内源性陶在多个部位被酸化
Ghadir Sindi1, Sazan Ismael1, Reaz Uddin1
1Neuroscience Program, Department of Biological Sciences, Ohio University, Athens, OH 45701, USA.
bioRxiv : the preprint server for biology
|June 10, 2024
概括
人类的神经产生细胞自发地释放蛋白. 神经元活动增加tau释放,这取决于GSK-3β酸化,为阿尔茨海默氏症 (AD) 病理学提供了洞察力.
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
- 生物化学 生物化学
背景情况:
- 陶蛋白主要是细胞内,但可以在细胞外释放,在阿尔茨海默氏症 (AD) 病理学中发挥作用.
- 释放的机制,特别是在人类神经元的生理条件下,还不太清楚.
研究的目的:
- 在生理条件下,研究从人类神经产生细胞 (ReNCell VM) 中内源性释放.
- 描述活动依赖的的释放,并确定关键的酸化部位和调节途径.
主要方法:
- 利用ReNCell VM,一个人类神经产生细胞系,研究内源性tau释放.
- 用AMPA或KCl刺激细胞以诱导活动依赖的tau释放.
- 使用特异性抗体分析的酸化状态,并评估GSK-3β抑制的影响.
主要成果:
- 在生理条件下,Tau自发地从ReNCell VM细胞中释放出来.
- 神经元活动显著增加了tau的释放,其中特定的酸化位 (例如T175/T181,S202/T205) 是至关重要的.
- 抑制GSK-3β显著降低了依赖活动的tau释放,突出显示了它在该过程中的作用.
结论:
- ReNCell VM是研究人类神经元细胞中生理性释放的合适模型.
- 活动依赖的释放受GSK-3β依赖酸化的调节.
- 了解这些释放机制对于理解阿尔茨海默病的进展至关重要.
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