The role of metals in beta-amyloid peptide aggregation: X-Ray spectroscopy and numerical simulations.
The role of metals in beta-amyloid peptide aggregation: X-Ray spectroscopy and numerical simulations.
复制标题
金属在 β-淀粉样肽聚集中的作用：X 射线光谱和数值模拟。
DOI：
10.2174/156720508786898505
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发表时间：
2008
影响因子：
2.1
通讯作者：
S. Morante
中科院分区：
文献类型：
--
作者：
S. Morante
这篇综述的目的是展示如何通过现代光谱技术和先进的第一性原理数值模拟的结合，成功地研究淀粉样蛋白病理斑块形成的起源——蛋白质错误折叠和聚集的物理化学基础。在以细胞外纤维物质沉积和一般称为淀粉样变性为特征的大量疾病（超过20种）中，我们将重点关注阿尔茨海默病，这是一种进行性和破坏性的神经退行性病理，影响了世界上很大一部分老年人口。鉴定好的多肽（即所谓的β -多肽）在疾病发展过程中经历错误折叠过程。一个重要的，但尚未完全阐明，rôle似乎在这些过程中起作用的过渡金属（主要是铜和锌），已观察到大量存在于患者的神经斑块。从这一观察开始，关于相关金属-肽结合位点的结构特性的一些有趣的结果，从x射线吸收光谱实验和Car-Parrinello类型的从头算分子动力学模拟之间的相互作用中出现，将被报道和讨论。
The aim of this review is to show how the challenging problem of understanding the physico-chemical basis of protein misfolding and aggregation which are at the origin of plaque formation in amyloid pathologies can be successfully investigated with a combination of modern spectroscopic techniques and advanced first principle numerical simulations. Within the vast group of diseases (more than 20) characterized by extra-cellular deposition of fibrillar material and generically called Amyloidosis, we shall focus on the Alzheimer's disease, a progressive and devastating neurodegenerative pathology affecting an important fraction of the world aged population. Well identified peptides (the so called Abeta-peptides) undergo a misfolding process during the development of the disease. An important, but not yet fully elucidated, rôle appears to be played in these processes by transition metals (mainly copper and zinc) that have been observed to be present in large amounts in patient's neurological plaques. Starting from this observation, a number of interesting results concerning the structural properties of the relevant metal-peptide binding site, emerging from the interplay between X-ray Absorption Spectroscopy experiments, and ab initio molecular dynamics simulations of the Car-Parrinello type will be reported and discussed.