Department of Chemistry and Applied Biosciences, ETH Zurich, 8093, Zurich (CH), Switzerland.
Pharm Res. 2017 Dec;34(12):2628-2636. doi: 10.1007/s11095-017-2266-4. Epub 2017 Sep 28.
An increasing amount of findings suggests that the aggregation of soluble peptides and proteins into amyloid fibrils is a relevant upstream process in the complex cascade of events leading to the pathology of Alzheimer's disease and several other neurodegenerative disorders. Nevertheless, several aspects of the correlation between the aggregation process and the onset and development of the pathology remain largely elusive. In this context, biophysical and biochemical studies in test tubes have proven extremely powerful in providing quantitative information about the structure and the reactivity of amyloids at the molecular level. In this review we use selected recent examples to illustrate the importance of such biophysical research to complement phenomenological studies based on cellular and molecular biology, and we discuss the implications for pharmaceutical applications associated with Alzheimer's disease and other neurodegenerative disorders in both academic and industrial contexts.
越来越多的研究结果表明,可溶性肽和蛋白质聚集成淀粉样纤维是导致阿尔茨海默病和几种其他神经退行性疾病病理的复杂级联事件的相关上游过程。然而,聚合过程与发病和发展之间的相关性的几个方面在很大程度上仍然难以捉摸。在这种情况下,试管中的生物物理和生化研究已被证明在提供有关淀粉样蛋白在分子水平上的结构和反应性的定量信息方面非常有效。在这篇综述中,我们使用选定的最近的例子来说明这种生物物理研究的重要性,以补充基于细胞和分子生物学的现象学研究,我们还讨论了与阿尔茨海默病和其他神经退行性疾病相关的制药应用的影响,无论是在学术还是工业环境中。