Quantitative proteomics analysis of phosphorylated proteins in the hippocampus of Alzheimer's disease subjects

被引:83
|
作者
Di Domenico, Fabio [1 ,2 ]
Sultana, Rukhsana [1 ]
Barone, Eugenio [1 ,3 ]
Perluigi, Marzia [2 ]
Cini, Chiara [2 ,4 ]
Mancuso, Cesare [3 ]
Cai, Jian [5 ]
Pierce, William M. [5 ]
Butterfield, D. Allan [1 ]
机构
[1] Univ Kentucky, Dept Chem, Ctr Membrane Sci, Sanders Brown Ctr Aging, Lexington, KY 40506 USA
[2] Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy
[3] Catholic Univ, Sch Med, Inst Pharmacol, I-00168 Rome, Italy
[4] CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy
[5] Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA
关键词
Alzheimer's disease; Protein phosphorylation; Phosphoproteomics; 2-DE; MILD COGNITIVE IMPAIRMENT; FIBRILLARY ACIDIC PROTEIN; PAIRED HELICAL FILAMENTS; OXIDATIVELY MODIFIED PROTEINS; INFERIOR PARIETAL LOBULE; CREATINE-KINASE BB; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; PHOSPHOPROTEOMIC ANALYSIS; TRANSGENIC MICE; 6-PHOSPHOGLUCONATE DEHYDROGENASE;
D O I
10.1016/j.jprot.2011.03.033
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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's 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 quantitative 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. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:1091 / 1103
页数:13
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