Stability matters, too - the thermodynamics of amyloid fibril formation.

Stability matters, too - the thermodynamics of amyloid fibril formation.
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DOI:
10.1039/d1sc06782f
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发表时间:
2022-09-14
期刊:
影响因子:
8.4
通讯作者:
Buell, Alexander K.
Buell, Alexander K.
中科院分区:
化学1区
文献类型:
--
作者:
Buell, Alexander K.

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淀粉样原纤维是蛋白质的超分子均聚物,在生物学功能和疾病中发挥重要作用。在过去的几十年里,这些物体受到了指数级增长的关注,这是由于它们在一系列严重疾病的病因学中所起的作用,最明显的是一些神经退行性疾病。虽然存在大量的实验研究来研究淀粉样蛋白原纤维的形成方式和速度,以及如何抑制它们的形成,但实验工作的更有限的主体试图回答为什么这些类型的结构形成(即热力学驱动力)以及它们实际上有多稳定的问题。在这篇综述中,我试图给出一个概述的类型的实验,迄今已进行回答这些问题,并总结我们目前的理解淀粉样蛋白热力学。与动力学研究相比,淀粉样蛋白形成的热力学在很大程度上被忽视了。在这篇评论中,目前的状态的实验探索淀粉样蛋白热力学和重要的开放问题突出。
Amyloid fibrils are supramolecular homopolymers of proteins that play important roles in biological functions and disease. These objects have received an exponential increase in attention during the last few decades, due to their role in the aetiology of a range of severe disorders, most notably some of a neurodegenerative nature. While an overwhelming number of experimental studies exist that investigate how, and how fast, amyloid fibrils form and how their formation can be inhibited, a much more limited body of experimental work attempts to answer the question as to why these types of structures form (i.e. the thermodynamic driving force) and how stable they actually are. In this review, I attempt to give an overview of the types of experiments that have been performed to-date to answer these questions, and to summarise our current understanding of amyloid thermodynamics. The thermodynamics of amyloid formation has largely been neglected compared to kinetic studies. In this review, the current state of the experimental exploration of amyloid thermodynamics is presented and important open questions are highlighted.
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