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使用竞争筛选方法筛选识别α-突触核蛋白寡聚物的 DNA 适体。

Selection of DNA aptamers that recognize α-synuclein oligomers using a competitive screening method.

机构信息

Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo, Japan.

出版信息

Anal Chem. 2012 Jul 3;84(13):5542-7. doi: 10.1021/ac300330g. Epub 2012 Jun 12.

DOI:10.1021/ac300330g
PMID:22697251
Abstract

α-Synuclein (α-syn) oligomers are considered major molecules responsible for the onset of Parkinson's disease and dementia with Lewy bodies. α-Syn oligomers thus serve as an important target for the development of drugs and diagnostic tests for neurodegenerative diseases. In this paper we report on the identification of DNA aptamers that bind to soluble α-syn oligomers. A competitive screening method based on aptamer blotting was used for the selection of α-syn oligomer-specific aptamers. This approach resulted in the identification of eight aptamers that specifically bind to α-syn oligomers among α-syn monomers, oligomers, and fibrils. Interestingly, the aptamers also bound to amyloid β oligomers, which are strongly associated with the development of Alzheimer's disease. The results of this study support the hypothesis that amyloid oligomers share a common structure. Oligomer-binding aptamers may serve as powerful analytical tools for the design and development of drugs and diagnostic tests for neurodegenerative diseases.

摘要

α-突触核蛋白(α-syn)寡聚体被认为是导致帕金森病和路易体痴呆的主要分子。因此,α-syn 寡聚体是开发神经退行性疾病药物和诊断测试的重要靶点。在本文中,我们报告了鉴定与可溶性 α-syn 寡聚体结合的 DNA 适体的情况。基于适体印迹的竞争性筛选方法用于选择 α-syn 寡聚体特异性适体。该方法鉴定了 8 个适体,它们在 α-syn 单体、寡聚体和原纤维中特异性结合 α-syn 寡聚体。有趣的是,这些适体也与与阿尔茨海默病的发展密切相关的淀粉样 β 寡聚体结合。这项研究的结果支持了这样一种假说,即淀粉样寡聚体具有共同的结构。寡聚体结合适体可能成为设计和开发神经退行性疾病药物和诊断测试的有力分析工具。

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