The Amyloid Phenomenon and Its Links with Human Disease
The Amyloid Phenomenon and Its Links with Human Disease
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DOI：
10.1101/cshperspect.a023648
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发表时间：
2017-06-01
影响因子：
7.2
通讯作者：
Dobson, Christopher M.
中科院分区：
文献类型：
--
作者：
Dobson, Christopher M.
通常可溶性蛋白质转化为淀粉样纤维的能力现在被认为是一种普遍现象。这种结构的核心元件的总体交叉β结构对于不同的氨基酸序列是非常相似的，因为这种结构由与共同多肽主链相关的相互作用主导。相反，蛋白质功能状态的复杂和错综复杂的结构的多样性由涉及可变侧链的特定相互作用决定，其序列对于给定的蛋白质是独特的。然而，侧链决定了淀粉样蛋白结构的重要方面，包括形成原纤维核心元件的序列区域以及转化过程的动力学和机制。蛋白质的淀粉样状态的形成在包括阿尔茨海默病和帕金森病以及2型糖尿病的一系列医学病症的背景下是特别重要的。这些疾病在现代世界变得越来越普遍，主要是由于寿命延长和生活方式改变的结果，现在影响到全世界约5亿人。本文综述了我们对这些疾病的分子起源的理解的最新进展，并讨论了新的和合理的治疗策略，以打击他们的发病和进展的新想法。
The ability of normally soluble proteins to convert into amyloid fibrils is now recognized to be a generic phenomenon. The overall cross-beta architecture of the core elements of such structures is closely similar for different amino acid sequences, as this architecture is dominated by interactions associated with the common polypeptide main chain. In contrast, the multiplicity of complex and intricate structures of the functional states of proteins is dictated by specific interactions involving the variable side chains, the sequence of which is unique to a given protein. Nevertheless, the side chains dictate important aspects of the amyloid structure, including the regions of the sequence that form the core elements of the fibrils and the kinetics and mechanism of the conversion process. The formation of the amyloid state of proteins is of particular importance in the context of a range of medical disorders that include Alzheimer's and Parkinson's diseases and type 2 diabetes. These disorders are becoming increasingly common in the modern world, primarily as a consequence of increasing life spans and changing lifestyles, and now affect some 500 million people worldwide. This review describes recent progress in our understanding of the molecular origins of these conditions and discusses emerging ideas for new and rational therapeutic strategies by which to combat their onset and progression.