Analyzing the aggregation of polyglutamine-expansion proteins and its modulation by molecular chaperones.
Analyzing the aggregation of polyglutamine-expansion proteins and its modulation by molecular chaperones.
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DOI：
10.1016/j.ymeth.2010.12.035
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发表时间：
2011-03
期刊：
影响因子：
4.8
通讯作者：
H. Kubota;Akira Kitamura;K. Nagata
中科院分区：
文献类型：
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作者：
H. Kubota;Akira Kitamura;K. Nagata
多聚谷氨酰胺(PolyQ)膨胀蛋白可导致蛋白质聚集在神经细胞的胞浆和胞核中，导致神经退行性疾病。例如，Huntingtin(HTT)蛋白中多聚Q区(>；40重复)的扩展导致亨廷顿病，而多聚Q扩展的ataxin导致几种类型的共济失调。在患者的神经细胞中发现富含多聚Q的包涵体，提示多聚Q病是由蛋白质错误折叠引起的。然而，PolyQ-Expansion蛋白发挥神经元毒性的机制在很大程度上还不清楚。在这里，我们回顾了分析分子伴侣在防止多聚Q聚集和毒性中的作用以及测量多聚Q聚集的特征和动力学的实验方法，特别是着重于荧光标记的多聚Q扩展蛋白的细胞模型和动态成像以及伴侣对它们的调节。
Polyglutamine (polyQ)-expansion proteins cause protein aggregation in the cytosol and nucleus of neuronal cells, leading to neurodegenerative diseases. For example, expansion of the polyQ tract (>40 repeats) in huntingtin (htt) proteins leads to Huntington disease, while polyQ-expanded ataxins cause several types of ataxias. PolyQ-rich inclusions are found in neuronal cells of patients, suggesting that polyQ disease is caused by protein misfolding. However, the mechanisms by which polyQ-expansion proteins exert neuronal toxicity are largely unknown. Here, we review experimental procedures to analyze the roles of molecular chaperones in preventing polyQ aggregation and toxicity as well as to measure the characteristics and dynamics of polyQ aggregation, particularly focusing on cellular models and dynamic imaging of fluorescently-labeled polyQ-expansion proteins and their modulation by chaperones.