在衰老和阿尔茨海默病中休息和抗压力
Tao Lu1, Liviu Aron1, Joseph Zullo1
1Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|March 28, 2014
概括
抑制素1-沉默转录因子 (REST) 对于在衰老过程中保持神经元功能和预防神经退行至关重要. 休息的丧失与认知衰退和阿尔茨海默病有关,强调其神经保护作用.
科学领域:
- 神经科学是一个神经科学.
- 衰老研究研究 衰老研究
- 分子生物学分子生物学
背景情况:
- 在衰老过程中保护神经元功能和防止神经退行的机制在很大程度上是未知的.
- 压抑元件1-沉默转录因子 (REST) 在神经元发育和功能中起作用.
研究的目的:
- 研究REST在正常人脑衰老中的作用及其与神经退行性疾病的关联.
- 阐明REST影响神经元存活并防止与年龄相关的功能障碍的分子机制.
主要方法:
- 从老年人和认知障碍患者的人类神经元中分析REST表达.
- 用深度测序 (ChIP-seq) 进行染色体免疫沉,以识别REST调控基因.
- 在小鼠模型和C. elegans中进行的研究,以评估REST删除或其正义词的功能影响.
主要成果:
- 休息在正常衰老的人类神经元中被普遍诱导,但在轻度认知障碍和阿尔茨海默氏症中失去了.
- 休息抑制促进细胞死亡和阿尔茨海默病理学的基因,同时诱导应激反应基因.
- 休息保护神经元免受氧化应激和粉样β毒性;其删除导致与年龄有关的神经退行.
结论:
- 休息激活是衰老和认知保存期间神经保护的关键机制.
- 休息功能的丧失有助于老化中的神经退行以及阿尔茨海默病.
- 休息水平与认知功能和寿命相关,表明其作为治疗点的潜力.
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