Self-propagating, molecular-level polymorphism in Alzheimer's β-amyloid fibrils
Self-propagating, molecular-level polymorphism in Alzheimer's β-amyloid fibrils
复制标题
DOI：
10.1126/science.1105850
复制
发表时间：
2005-01-14
期刊：
影响因子：
56.9
通讯作者：
Tycko, R
中科院分区：
文献类型：
--
作者：
Petkova, AT;Leapman, RD;Tycko, R
淀粉样原纤维通常在电子显微镜和原子力显微镜图像中表现出多种不同的形态，通常在单个图像场中。通过使用电子显微镜和固态核磁共振测量阿尔茨海默病的40个残基的β-淀粉样肽形成的纤维，（Abeta（1-40）），我们表明不同的原纤维形态具有不同的潜在分子结构，主要结构可以通过原纤维生长条件的细微变化来控制，并且当原纤维从预先形成的种子生长时，形态和分子结构都是自传播的。不同的Abeta（1-40）原纤维形态在神经元细胞培养物中也具有显著不同的毒性。这些结果对淀粉样蛋白形成的机制、朊病毒疾病中的菌株现象、淀粉样蛋白原纤维在淀粉样蛋白疾病中的作用以及基于淀粉样蛋白的纳米材料的开发具有启示。
Amyloid fibrils commonly exhibit multiple distinct morphologies in electron microscope and atomic force microscope images, often within a single image field. By using electron microscopy and solid-state nuclear magnetic resonance measurements on fibrils formed by the 40-residue beta-amyloid peptide of Alzheimer's disease (Abeta(1-40)), we show that different fibril morphologies have different underlying molecular structures, that the predominant structure can be controlled by subtle variations in fibril growth conditions, and that both morphology and molecular structure are self-propagating when fibrils grow from preformed seeds. Different Abeta(1-40) fibril morphologies also have significantly different toxicities in neuronal cell cultures. These results have implications for the mechanism of amyloid formation, the phenomenon of strains in prion diseases, the role of amyloid fibrils in amyloid diseases, and the development of amyloid-based nanomaterials.