一个PrPEGFR信号轴通过调节细胞能量通路来控制神经干细胞衰老
Bradley R Groveman1, Benjamin Schwarz2, Eric Bohrnsen2
1Laboratory of Neurological Infections and Immunity, National Institute of Allergy and Infectious Diseases, Division of Intramural Research, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, Montana, USA.
The Journal of biological chemistry
|October 6, 2023
概括
蛋白 (PrP) 缺失通过降低表皮生长因子受体 (EGFR) 信号和线粒体功能来损害神经干细胞 (NSC) 的生长,导致增殖减少和衰老增加.
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:
- 尽管它与神经退行性疾病有关,但对蛋白 (PrP) 的原生功能知之甚少.
- PrP影响细胞增殖,衰老和表皮生长因子受体 (EGFR) 信号传递.
- 成人神经干细胞 (NSC) 对大脑可塑性至关重要,但它们通过PrP的调节尚不清楚.
研究的目的:
- 研究PrP在调节细胞衰老,EGFR信号传递和成年小鼠神经干细胞 (NSC) 中线粒体功能中的作用.
主要方法:
- 在实验室中对PrP淘汰赛 (KO) 和野生型 (WT) 的NSC进行比较.
- 分析EGFR信号传递,细胞衰老标志物和线粒体功能.
- 细胞能量通路的RNA测序和代谢分析.
主要成果:
- 与WT NSC相比,PrP KO NSCs表现出减少的增殖和增加的衰老.
- 在PrP KO NSC中,EGFR表达减少,而EGF补充剂减轻了衰老.
- RNA-seq和代谢分析揭示了PrP KO NSC中EGFR信号的下调,线粒体功能的降低和能量代谢受损.
结论:
- 蛋白 (PrP) 对于维持神经干细胞 (NSC) 增殖和功能至关重要.
- 缺少PrP会导致EGFR信号受损,线粒体能量产生减少,细胞衰老.
- 这些发现表明,PrP在通过能量代谢和信号传递来调节NSC生长途径方面发挥着关键作用.
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