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Illuminating amyloid fibrils: Fluorescence-based single-molecule approaches
Computational and Structural Biotechnology Journal ( IF 4.4 ) Pub Date : 2021-08-13 , DOI: 10.1016/j.csbj.2021.08.017
Lauren J Rice 1, 2 , Heath Ecroyd 1, 2 , Antoine M van Oijen 1, 2
Affiliation  

The aggregation of proteins into insoluble filamentous amyloid fibrils is a pathological hallmark of neurodegenerative diseases that include Parkinson’s disease and Alzheimer’s disease. Since the identification of amyloid fibrils and their association with disease, there has been much work to describe the process by which fibrils form and interact with other proteins. However, due to the dynamic nature of fibril formation and the transient and heterogeneous nature of the intermediates produced, it can be challenging to examine these processes using techniques that rely on traditional ensemble-based measurements. Single-molecule approaches overcome these limitations as rare and short-lived species within a population can be individually studied. Fluorescence-based single-molecule methods have proven to be particularly useful for the study of amyloid fibril formation. In this review, we discuss the use of different experimental single-molecule fluorescence microscopy approaches to study amyloid fibrils and their interaction with other proteins, in particular molecular chaperones. We highlight the mechanistic insights these single-molecule techniques have already provided in our understanding of how fibrils form, and comment on their potential future use in studying amyloid fibrils and their intermediates.

中文翻译:


照亮淀粉样原纤维:基于荧光的单分子方法



蛋白质聚集成不溶性丝状淀粉样原纤维是包括帕金森病和阿尔茨海默病在内的神经退行性疾病的病理标志。自从淀粉样原纤维的鉴定及其与疾病的关联以来,已经有很多工作来描述原纤维形成以及与其他蛋白质相互作用的过程。然而,由于原纤维形成的动态性质以及所产生的中间体的瞬态和异质性质,使用依赖于传统的基于集合的测量的技术来检查这些过程可能具有挑战性。单分子方法克服了这些限制,因为可以单独研究种群内的稀有和短命物种。基于荧光的单分子方法已被证明对于淀粉样原纤维形成的研究特别有用。在这篇综述中,我们讨论了使用不同的实验单分子荧光显微镜方法来研究淀粉样原纤维及其与其他蛋白质(特别是分子伴侣)的相互作用。我们强调这些单分子技术已经为我们理解原纤维如何形成提供了机制见解,并评论了它们在研究淀粉样蛋白原纤维及其中间体中的未来潜在用途。
更新日期:2021-08-13
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