爱荷华州突变β-粉样纤维的结构演变,在重复播种生长下,从多态变异到同质状态
Wei Qiang1, Wai-Ming Yau, Robert Tycko
1Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, United States.
Journal of the American Chemical Society
|March 2, 2011
概括
阿尔茨海默病 (AD) 纤维的结构变异可以使用重复播种协议来选择. 这种方法隔离了单个纤维结构,揭示了对生长条件的敏感性以及对粉样纤维研究的含义.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 神经科学是一个神经科学.
背景情况:
- β-粉样 (Aβ) 纤维的结构多态性与阿尔茨海默病 (AD) 病原发生有关.
- 了解纤维结构对于开发有效的AD疗法至关重要.
- 与家族性AD相关的D23N-Aβ1-40) 突变体表现出纤维细胞多态性.
研究的目的:
- 开发和验证一个重复播种协议,用于选择同质的Aβ纤维结构.
- 在受控条件下研究D23N-Aβ(1-40) 纤维的结构演变和稳定性.
- 评估结构变异对硫黄素T (ThT) 光效应的影响.
主要方法:
- 为纤维细胞放大重复播种协议.
- 提奥夫拉T (ThT) 光光谱学.
- 传输电子显微镜 (TEM). 传输电子显微镜.
- 固态核磁共振 (NMR) 是一种固态核磁共振技术.
主要成果:
- 重复播种有选择地从多态混合物中放大一个单一的,均的D23N-Aβ(1-40) 纤维结构.
- 放大纤维结构对pH,温度和动荡等环境因素敏感.
- 最终的纤维结构主要采用平行β-sheet配置,表明反平行结构的转移稳定性.
- ThT光强度高度依赖于纤维结构的变化,即使是相同的多.
结论:
- 一个重复的播种协议可以有效地隔离特定的Aβ纤维素多态.
- 环境条件显著影响D23N-Aβ1-40) 纤维的最终结构.
- 在Aβ纤维中的反平行β片结构可能是短暂的.
- ThT光的可变性强调了在粉样蛋白研究中需要仔细解释的必要性.
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