FTIR spectroscopic imaging of protein aggregation in living cells.
FTIR spectroscopic imaging of protein aggregation in living cells.
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DOI：
10.1016/j.bbamem.2013.01.014
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发表时间：
2013-10
影响因子：
3.4
通讯作者：
Smith, Randy J.
中科院分区：
文献类型：
--
作者：
Miller, Lisa M.;Bourassa, Megan W.;Smith, Randy J.
关键词：
蛋白质错误折叠和聚集是许多疾病的特征，包括阿尔茨海默病、帕金森氏病、亨廷顿病、肌萎缩侧索硬化症和普里恩病。在所有情况下，一种自然产生的蛋白质错误折叠并形成聚集体，被认为通过一系列尚未完全解开的机制扰乱细胞功能。傅里叶变换红外光谱(FTIR)是一种对蛋白质二级结构敏感的光谱技术，已被广泛用于研究蛋白质的错误折叠和聚集体形成过程。本文主要介绍FTIR光谱技术和光谱显微镜技术如何在体外和直接在细胞和组织内评价疾病相关蛋白的结构变化。最后，将介绍正在进行的技术进步，使蛋白质聚集直接在活细胞内的时间分辨FTIR成像成为可能，这可以提供与聚集形成相关的结构中间体、时间尺度和细胞毒性机制的洞察。
Protein misfolding and aggregation are the hallmark of a number of diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and the prion diseases. In all cases, a naturally-occurring protein misfolds and forms aggregates that are thought to disrupt cell function through a wide range of mechanisms that are yet to be fully unraveled. Fourier transform infrared (FTIR) spectroscopy is a technique that is sensitive to the secondary structure of proteins and has been widely used to investigate the process of misfolding and aggregate formation. This review focuses on how FTIR spectroscopy and spectroscopic microscopy are being used to evaluate the structural changes in disease-related proteins both in vitro and directly within cells and tissues. Finally, ongoing technological advances will be presented that are enabling time-resolved FTIR imaging of protein aggregation directly within living cells, which can provide insight into the structural intermediates, time scale, and mechanisms of cell toxicity associated with aggregate formation.
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