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线粒体蛋白与淀粉样β肽之间的直接相互作用及其对阿尔茨海默病进展和治疗的意义。

A Direct Interaction Between Mitochondrial Proteins and Amyloid-β Peptide and its Significance for the Progression and Treatment of Alzheimer’s Disease.

作者信息

Benek Ondrej, Aitken Laura, Hroch Lukas, Kuca Kamil, Gunn-Moore Frank, Musilek Kamil

机构信息

: University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic..

出版信息

Curr Med Chem. 2015 Feb 26;22(9):1056 - 1085. doi: 10.2174/0929867322666150114163051.

Abstract

The amyloid-β peptide (Aβ) has been associated with Alzheimer's disease (AD) for decades. The original amyloid cascade hypothesis declared that the insoluble extracellular plaques were responsible for Aβ toxicity. Later, this hypothesis has been updated and soluble intracellular Aβ forms and their effects within the cell have come into focus.Mitochondrial dysfunction plays an important role in the pathophysiology of AD. Aβ was detected inside mitochondria and several mitochondrial proteins were found to interact directly with Aβ. Such interactionscan affecta protein's function and cause damage to the mitochondria and finally to the whole cell.This review summarizes the current knowledge of mitochondrial proteins directly interacting with Aβ and discusses their significance for the development of therapeutics in the treatment of AD.

摘要

几十年来,β淀粉样肽(Aβ)一直与阿尔茨海默病(AD)相关。最初的淀粉样蛋白级联假说宣称,不溶性细胞外斑块是Aβ毒性的原因。后来,这一假说得到了更新,可溶性细胞内Aβ形式及其在细胞内的作用成为了研究重点。线粒体功能障碍在AD的病理生理学中起着重要作用。在线粒体内检测到了Aβ,并且发现几种线粒体蛋白直接与Aβ相互作用。这种相互作用会影响蛋白质的功能,对线粒体乃至整个细胞造成损害。本综述总结了目前关于直接与Aβ相互作用的线粒体蛋白的知识,并讨论了它们在AD治疗药物开发中的意义。

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