轴突合成的ATF4通过大脑区域传递神经退行信号
Jimena Baleriola1, Chandler A Walker2, Ying Y Jean3
1The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Cell
|August 30, 2014
概括
阿尔茨海默病 (AD) 病理通过局部蛋白质合成通过轴突传播. 转录因子ATF4调解了这一过程,为AD治疗提供了一个新的点.
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
- 病理学 病理学 病理学
背景情况:
- 阿尔茨海默病 (AD) 涉及向后扩散的轴突损伤.
- 这种病理传播背后的机制在很大程度上是未知的.
研究的目的:
- 研究轴突蛋白合成在AD神经退行症中的作用.
- 为了确定负责AD病理的逆行传播的分子媒介.
主要方法:
- 粉样β (Aβ1-42) 在体外和体内对轴突的局部应用.
- 抑制局部轴突转换和逆行运输.
- 使用siRNA的轴突中ATF4mRNA的淘汰.
- 在小鼠模型和人类AD大脑样本中分析蛋白质合成和ATF4表达.
主要成果:
- 当地应用的Aβ1-42触发了轴突蛋白质合成,包括转录因子ATF4.4.
- 抑制轴突转化或ATF4消除了Aβ诱导的神经元损失.
- 在小鼠中注射Aβ1-42导致前脑神经元损失,与高调的轴突蛋白质合成和ATF4mRNA.
- 在阿尔茨海默病患者大脑中的轴突中发现了ATF4.
结论:
- 轴内转换在阿尔茨海默氏症神经退行症中起着积极的作用.
- ATF4作为AD病理沿轴突传播的关键调解者.
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