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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
的树突功能调解阿尔茨海默病小鼠模型中的粉样β毒性
Lars M Ittner1, Yazi D Ke, Fabien Delerue
1Alzheimer's and Parkinson's Disease Laboratory, Brain and Mind Research Institute, University of Sydney, Sydney NSW 2050, Australia. littner@med.usyd.edu.au
Cell
|July 27, 2010
概括
阿尔茨海默病 (AD) 涉及粉样β和. 这项研究揭示了.
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) 病理学涉及大脑中的粉样β (Abeta) 和蛋白聚合.
- 关联阿贝塔毒性与tau的确切机制仍然不完全理解.
- 蛋白主要被称为轴突蛋白,但其在突触中的作用正在研究中.
研究的目的:
- 阐明tau和阿贝塔毒性在突触后水平之间的机械联系.
- 调查在Src 激酶 Fyn. 的 postsynaptic 向中的作用.
- 在阿尔茨海默病模型中评估针对Fyn介导途径的治疗潜力.
主要方法:
- 使用的转基因小鼠模型:截断的tau (Deltatau) 和tau淘汰 (tau(-/-)) 的小鼠.
- 研究了Fyn激酶及其基质NMDA受体 (NR) 的突触后向.
- 在阿贝塔形成的APP23小鼠中评估记忆缺陷和存活率,具有改变的tau表达.
- 在体内使用来破坏NR和PSD-95之间的Fyn介导相互作用.
主要成果:
- 的错误分离或缺失破坏了Fyn激酶的突触后向.
- 破坏Fyn向未结合的NMDA受体介导的兴奋毒性,减轻阿贝塔毒性.
- 在APP23小鼠中,delta表达和tau缺陷挽救了记忆缺陷,并改善了生存率.
- 针对Fyn-NR-PSD-95相互作用的酸完全挽救了与AD相关的缺陷.
结论:
- 陶蛋白在Fyn激酶的 postsynaptic 向中起着关键的树突性作用.
- 这种tau功能在突触后调解阿贝塔毒性,有助于阿尔茨海默病的发病.
- 向tau-Fyn-NMDA受体通路为阿尔茨海默病提供了一个有前途的治疗策略.
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