Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
J Neurochem. 2021 Oct;159(2):318-329. doi: 10.1111/jnc.15298. Epub 2021 Feb 2.
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.
基于质谱（MS）的稳定同位素标记蛋白质组学分析已成为评估蛋白质稳态水平、蛋白质周转和蛋白质定位的有力策略。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。最近，稳定同位素-MS 已被用于研究阿尔茨海默病 (AD) 的早期病理机制，以及具有 AD 样病理学的小鼠模型。在这篇综述中，我们总结了这些稳定同位素-MS 实验设计以及最近在 AD 病理学背景下的应用。我们还描述了我们目前利用 AD 小鼠模型大脑中稳定同位素标记淀粉样纤维的核磁共振（NMR）分析的努力。总的来说，这些方法为通过阐明治疗和预防的靶点机制来研究 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。
