RT-QuIC-based detection of alpha-synuclein seeding activity in brains of dementia with Lewy Body patients and of a transgenic mouse model of synucleinopathy.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Jung-Youn Han, Hyung-Sup Jang, Alison J E Green, Young Pyo Choi
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引用次数: 19

Abstract

RT-QuIC is a shaking-based cyclic amplification technique originally developed in the prion field to detect minute amounts of scrapie prion protein (PrPSc). In this study, we applied the RT-QuIC assay to investigate a-synuclein (a-syn) seeding activity in brains of Dementia with Lewy Body (DLB) patients and in brains of G2-3 transgenic mice expressing human a-syn with A53T mutation. The results show that a-syn seeding activity varies between patients with detectable dilutions ranging from 10-3 to 10-8 dilutions of brain tissue and is stable under exposures to the cycles of freezing, thawing and sonication. A53T a-syn aggregates from G2-3 transgenic mice greatly favoured A53T recombinant human a-syn as substrates in comparison to wild-type a-syn, suggesting that conformations for wild-type a-syn to be able to adopt are not compatible with that of A53T aggregates from G2-3.

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基于rt - quic的路易体痴呆患者脑α -突触核蛋白播种活性检测及突触核蛋白病变转基因小鼠模型的建立。
RT-QuIC是一种基于振荡的循环扩增技术,最初是在朊病毒领域开发的,用于检测微量痒病朊病毒蛋白(PrPSc)。在本研究中,我们采用RT-QuIC法研究了a-突触核蛋白(a-syn)在路易体痴呆(DLB)患者的大脑和表达A53T突变的人a-syn的G2-3转基因小鼠的大脑中的种子活性。结果表明,a-syn的播种活性在10-3 ~ 10-8稀释度的脑组织中存在差异,并在冷冻、解冻和超声循环下保持稳定。与野生型a-syn相比,来自G2-3转基因小鼠的A53T a-syn聚集体更倾向于作为底物的A53T重组人a-syn,这表明野生型a-syn能够采用的构象与来自G2-3的A53T聚集体不兼容。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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