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目前对金属依赖性淀粉样β蛋白聚集和毒性的理解。

Current understanding of metal-dependent amyloid-β aggregation and toxicity.

作者信息

Yi Yelim, Lim Mi Hee

机构信息

Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Republic of Korea

出版信息

RSC Chem Biol. 2022 Nov 22;4(2):121-131. doi: 10.1039/d2cb00208f. eCollection 2023 Feb 8.

Abstract

The discovery of effective therapeutics targeting amyloid-β (Aβ) aggregates for Alzheimer's disease (AD) has been very challenging, which suggests its complicated etiology associated with multiple pathogenic elements. In AD-affected brains, highly concentrated metals, such as copper and zinc, are found in senile plaques mainly composed of Aβ aggregates. These metal ions are coordinated to Aβ and affect its aggregation and toxicity profiles. In this review, we illustrate the current view on molecular insights into the assembly of Aβ peptides in the absence and presence of metal ions as well as the effect of metal ions on their toxicity.

摘要

发现针对阿尔茨海默病(AD)中淀粉样β蛋白(Aβ)聚集体的有效治疗方法极具挑战性,这表明其病因复杂,涉及多种致病因素。在受AD影响的大脑中,主要由Aβ聚集体组成的老年斑中发现了高浓度的金属,如铜和锌。这些金属离子与Aβ配位,影响其聚集和毒性特征。在这篇综述中,我们阐述了当前对于在有无金属离子情况下Aβ肽组装的分子见解以及金属离子对其毒性影响的观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db7/9906324/4764184c3198/d2cb00208f-f1.jpg

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