APP与DR6结合,通过独特的caspases触发轴突修剪和神经元死亡
Anatoly Nikolaev1, Todd McLaughlin, Dennis D M O'Leary
1Division of Research, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Nature
|February 20, 2009
概括
β-粉样蛋白前体蛋白 (APP) 和死亡受体6 (DR6) 触发了依赖于酶的神经元自我毁灭路径. 这条涉及酶6的途径对于轴突修剪至关重要,可能会导致阿尔茨海默病.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 发育生物学 发展生物学
背景情况:
- 轴突修剪和神经元细胞死亡对神经发育至关重要,但它们的机制尚不清楚.
- β-粉样蛋白前体蛋白 (APP) 和死亡受体6 (DR6) 都与神经元过程有关.
研究的目的:
- 阐明轴突修剪和神经元细胞死亡的机械基础.
- 调查APP和DR6在酶依赖的自我破坏途径中的作用.
主要方法:
- 在体内和体外研究中,使用了食物营养因子剥夺.
- 在突变小鼠中的功能损失和功能增益研究.
- 对酶激活模式和APP脱落的分析.
主要成果:
- 在发育中的神经元中,DR6对于轴突修剪和细胞体死亡至关重要.
- 轴突退化需要酶6,以点状模式激活.
- APP 作为 DR6 配体,其 N-终端片段 (N-APP) 在脱落时触发退化.
- 在突变小鼠中观察到神经肌肉结合表型.
结论:
- APP和DR6构成了神经元自我毁灭的途径.
- 一个细胞外APP片段,通过DR6和酶6,有助于神经退行和潜在的阿尔茨海默病.
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