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慢性创伤性脑病中的新型丝折叠包围了疏水分子
Benjamin Falcon1, Jasenko Zivanov1, Wenjuan Zhang1
1MRC Laboratory of Molecular Biology, Cambridge, UK.
Nature
|March 22, 2019
概括
研究人员确定了慢性创伤性脑病 (CTE) 中的丝结构. 这些结构是独一无二的,
科学领域:
- 神经科学
- 生物化学
- 病理学
背景情况:
- 慢性创伤性脑病 (CTE) 是一种与重复的头部冲击相关的渐进性神经退行性脑病.
- 目前诊断CTE需要解剖, 并且没有可用的疾病修饰疗法.
- 纤维的确切形态及其在CTE中形成的机制尚不清楚.
研究的目的:
- 确定CTE患者大脑中的高分辨率tau丝结构.
- 将CTE丝结构与阿尔茨海默氏症等其他神经退行性疾病中的结构进行比较.
- 在CTE中阐明tau聚合的结构基础.
主要方法:
- 使用冷电子显微镜分析了来自三个CTE大脑的丝.
- 在2.3 Å的分辨率下进行结构分析.
- 对已知的病进行了比较结构分析.
主要成果:
- 在CTE中,丝结构在所有三种病例中都是相同的,但与阿尔茨海默氏症和皮克氏症不同.
- 在CTE中,所有六个大脑tau异型组合成纤维,形成C形原纤维.
- 在CTE纤维中发现了独特的疏水腔和独特的原纤维接口,这表明辅因子参与.
结论:
- 确定的丝结构为CTE提供了统一的神经病理标准.
- 这些发现支持不同变异因子导致不同神经退行性疾病的假设.
- 了解这些结构可能为未来的CTE诊断和治疗策略铺平道路.
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