一个新的途径通过SIRT1和miR-134调节记忆和可塑性
Jun Gao1, Wen-Yuan Wang, Ying-Wei Mao
1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nature
|July 13, 2010
概括
SIRT1蛋白通过一种新的微RNA通路调节记忆和突触可塑性. 这一发现揭示了SIRT1在大脑功能中的新角色,与其细胞存活功能不同.
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
- 遗传学 是一个遗传学.
背景情况:
- 酵母Sir2的哺乳动物同类物SIRT1已知在心脏功能,DNA修复和基因组稳定性方面发挥作用.
- 新出现的证据表明SIRT1参与大脑生理学和神经系统疾病.
- 对于SIRT1在高阶大脑功能 (如认知) 中的作用,仍然在很大程度上未被探索.
研究的目的:
- 研究SIRT1在突触可塑性和记忆形成中的作用.
- 阐明潜在的分子机制,特别关注微RNA调节.
主要方法:
- 研究了SIRT1激活和功能丧失对突触可塑性的影响.
- 使用了涉及miR-134的微RNA介导机制及其对CREB和BDNF表达的调节.
- 在抑制器复合体中检查了SIRT1,YY1和miR-134之间的相互作用.
主要成果:
- 增强SIRT1的激活,而SIRT1的缺乏损害了突触可塑性和记忆形成.
- 这些效应是由特定于大脑的微RNA,miR-134调节的,该微RNA在转录后调节CREB表达.
- SIRT1通过涉及YY1的抑制器综合体限制miR-134的表达;SIRT1缺乏导致miR-134的增加,CREB和BDNF的减少以及塑性受损.
结论:
- 通过一种新的微RNA依赖途径,SIRT1在调节突触可塑性和记忆形成方面发挥着至关重要的作用.
- 这项研究确定了一种新机制,即SIRT1通过miR-134,CREB和BDNF调节认知,这与其细胞生存功能不同.
- SIRT1代表了影响认知功能的中枢神经系统疾病的潜在治疗标.
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