为何针对β淀粉样蛋白的研究未能为阿尔茨海默病带来新药？
Why Is Research on Amyloid-β Failing to Give New Drugs for Alzheimer's Disease?
作者信息
Doig Andrew J, Del Castillo-Frias Maria P, Berthoumieu Olivia, Tarus Bogdan, Nasica-Labouze Jessica, Sterpone Fabio, Nguyen Phuong H, Hooper Nigel M, Faller Peter, Derreumaux Philippe
机构信息
Department of Chemistry and Manchester Institute of Biotechnology, Faculty of Science and Engineering, University of Manchester , 131 Princess Street, Manchester M7 1DN, United Kingdom.
Biomaterials and Biology Chemistry, Institut de Chimie UMR7177, Université de Strasbourg , 4 rue B. Pascal, 67081 Strasbourg, France.
出版信息
ACS Chem Neurosci. 2017 Jul 19;8(7):1435-1437. doi: 10.1021/acschemneuro.7b00188. Epub 2017 Jun 6.
The two hallmarks of Alzheimer's disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1-40 and Aβ1-42. Targeting the production, aggregation, and toxicity of Aβ with small molecule drugs or antibodies is an active area of AD research due to the general acceptance of the amyloid cascade hypothesis, but thus far all drugs targeting Aβ have failed. From a review of the recent literature and our own experience based on in vitro, in silico, and in vivo studies, we present some reasons to explain this repetitive failure.
阿尔茨海默病（AD）的两个标志性特征是由高度磷酸化的tau蛋白聚集体构成的神经原纤维缠结（NFT）以及由淀粉样β（Aβ）肽（主要是Aβ1-40和Aβ1-42）组成的淀粉样斑块。由于淀粉样蛋白级联假说已被广泛接受，因此用小分子药物或抗体靶向Aβ的产生、聚集和毒性是AD研究的一个活跃领域，但迄今为止，所有靶向Aβ的药物均告失败。基于近期文献综述以及我们自身的体外、计算机模拟和体内研究经验，我们提出了一些理由来解释这种反复出现的失败情况。
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