Blackley H K, Sanders G H, Davies M C, Roberts C J, Tendler S J, Wilkinson M J
Laboratory of Biophysics and Surface Analysis, School of Pharmaceutical Sciences University of Nottingham, Nottingham, NG7 2RD, UK.
J Mol Biol. 2000 May 19;298(5):833-40. doi: 10.1006/jmbi.2000.3711.
We report the use of atomic force microscopy to observe the initial stages of beta-amyloid fibrillization in situ. The growth of individual beta-amyloid protofibrils on a mica substrate was followed over several hours. The first in situ visualization of protofibril formation from single aggregate units of beta-amyloid is reported. The growth of these protofibrils through the subsequent addition of these aggregate units is also observed. Growth of the protofibrils is bi-directional and the outgrowth of protofibrils from a common amyloid/heterogeneous core is also observed. Elongation also occurred by the addition of protofibrils from solution. This data provides an exciting insight into the early stages of beta-amyloid fibrillization and can be used to enhance the understanding of the mechanism(s) by which beta-amyloid fibrillizes and may consequently enable inhibition of one or more stages of fibrillization as a potential therapeutic strategy.
我们报告了使用原子力显微镜原位观察β-淀粉样蛋白纤维化的初始阶段。在云母基底上，对单个β-淀粉样蛋白原纤维的生长进行了数小时的跟踪观察。本文首次报道了从β-淀粉样蛋白的单个聚集单元原位可视化原纤维的形成过程。还观察到这些原纤维通过后续添加这些聚集单元而生长。原纤维的生长是双向的，并且还观察到原纤维从共同的淀粉样蛋白/异质核心向外生长。通过从溶液中添加原纤维也会发生伸长。这些数据为β-淀粉样蛋白纤维化的早期阶段提供了令人兴奋的见解，可用于增进对β-淀粉样蛋白纤维化机制的理解，并可能因此作为一种潜在的治疗策略，抑制纤维化的一个或多个阶段。
