Quantitative proteomics analysis of phosphorylated proteins in the hippocampus of Alzheimer's disease subjects.
Quantitative proteomics analysis of phosphorylated proteins in the hippocampus of Alzheimer's disease subjects.
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DOI：
10.1016/j.jprot.2011.03.033
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发表时间：
2011-06-10
影响因子：
3.3
通讯作者：
Butterfield, D. Allan
中科院分区：
文献类型：
--
作者：
Di Domenico, Fabio;Sultana, Rukhsana;Barone, Eugenio;Perluigi, Marzia;Cini, Chiara;Mancuso, Cesare;Cai, Jian;Pierce, William M.;Butterfield, D. Allan
酪氨酸、苏氨酸和丝氨酸残基的磷酸化是最重要的翻译后修饰之一，是多种需要蛋白激酶和蛋白磷酸酶严格控制的生物过程中细胞信号转导的关键调节因子。异常蛋白磷酸化与包括阿尔茨海默病（AD）在内的几种人类疾病有关。阿尔茨海默病的特征之一是存在神经原纤维缠结，由微管相关的异常过度磷酸化的tau蛋白组成。然而，其他一些蛋白在阿尔茨海默病中显示磷酸化水平的改变，这表明磷酸化失调可能有助于阿尔茨海默病的发病。磷酸化蛋白质组学作为一种定量和定性分析蛋白质磷酸化的有价值的方法近年来受到关注。我们使用荧光磷特异性Pro-Q钻石染料来鉴定AD与对照（CTR）受试者海马中显示其总体磷酸化改变的蛋白质。研究发现，参与关键神经元过程（如能量代谢或信号转导）的17种蛋白质发生了显著变化。这些磷酸化蛋白质组数据可能为更好地理解阿尔茨海默病发病和进展中不受调控的分子途径提供新的线索。
Phosphorylation on tyrosine, threonine and serine residues represents one of the most important post-translational modifications and is a key regulator of cellular signaling of multiple biological processes that require a strict control by protein kinases and protein phosphatases. Abnormal protein phosphorylation has been associated with several human diseases including Alzheimer disease (AD). One of the characteristic hallmarks of AD is the presence of neurofibrillary tangles, composed of microtubule-associated, abnormally hyperphosphorylated tau protein. However, several others proteins showed altered phosphorylation levels in AD suggesting that deregulated phosphorylation may contribute to AD pathogenesis. Phosphoproteomics has recently gained attention as a valuable approach to analyze protein phosphorylation, both in a quantitave and a qualitative way. We used the fluorescent phosphospecific Pro-Q Diamond dye to identify proteins that showed alterations in their overall phosphorylation in the hippocampus of AD vs. control (CTR) subjects. Significant changes were found for 17 proteins involved in crucial neuronal process such as energy metabolism or signal transduction. These phosphoproteome data may provide new clues to better understand molecular pathways that are deregulated in the pathogenesis and progression of AD.
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DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
4.1
作者：
DALLOCCHIO, F;MATTEUZZI, M;BELLINI, T
通讯作者：
BELLINI, T
影响因子：
7.4
作者：
Castegna, A;Aksenov, M;Butterfield, DA
通讯作者：
Butterfield, DA
影响因子：
4.7
作者：
Castegna, A;Aksenov, M;Butterfield, DA
通讯作者：
Butterfield, DA
影响因子：
21.3
作者：
Cohen, P
通讯作者：
Cohen, P