Using stable isotope labeling to advance our understanding of Alzheimer's disease etiology and pathology.

Using stable isotope labeling to advance our understanding of Alzheimer's disease etiology and pathology.
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DOI:
10.1111/jnc.15298
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发表时间:
2021-10
影响因子:
4.7
通讯作者:
Savas JN
Savas JN
中科院分区:
医学2区
文献类型:
--
作者:
Hark TJ;Savas JN

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稳定同位素标记与质谱(MS)为基础的蛋白质组学分析已成为一个强大的战略,以评估蛋白质稳态水平,蛋白质周转,蛋白质定位。将这些分析平台应用于神经退行性疾病可能会揭示这些毁灭性疾病病因的新方面。近年来,稳定同位素质谱已被用于研究阿尔茨海默病(AD)的早期病理机制与AD样病理小鼠模型。在这篇综述中,我们总结了这些稳定的同位素MS实验设计和最近的应用背景下,AD病理。我们还描述了我们目前的努力,旨在使用稳定的同位素标记的淀粉样蛋白原纤维从AD小鼠模型脑的核磁共振(NMR)分析。总的来说,这些方法通过阐明治疗和预防的靶向机制,为研究AD和其他神经退行性疾病中的蛋白质组变化提供了新的机会。
Stable isotope labeling with mass spectrometry (MS)-based proteomic analysis has become a powerful strategy to assess protein steady-state levels, protein turnover, and protein localization. Applying these analyses platforms to neurodegenerative disorders may uncover new aspects of the etiology of these devastating diseases. Recently, stable isotopes-MS has been used to investigate early pathological mechanisms of Alzheimer’s disease (AD) with mouse models of AD-like pathology. In this review, we summarize these stable isotope-MS experimental designs and the recent application in the context of AD pathology. We also describe our current efforts aimed at using nuclear magnetic resonance (NMR) analysis of stable isotope labeled amyloid fibrils from AD mouse model brains. Collectively, these methodologies offer new opportunities to study proteome changes in AD and other neurodegenerative diseases by elucidating mechanisms to target for treatment and prevention.
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