Abstract
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.
Original language | English |
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Pages (from-to) | 1091-1103 |
Number of pages | 13 |
Journal | Journal of Proteomics |
Volume | 74 |
Issue number | 7 |
DOIs | |
State | Published - Jun 10 2011 |
Bibliographical note
Funding Information:This work was supported in part by a NIH grant to D.A.B. [ AG-05119 ]. F.D.D. was supported by a Fellowship from Istituto Pasteur — Fondazione Cenci Bolognetti. We are grateful to the Neuropathology Core of the University of Kentucky Alzheimer's Disease Clinical Center for providing well-characterized specimens for this research. The authors declare no financial/commercial conflicts of interests with the results of this study.
Keywords
- 2-DE
- Alzheimer's disease
- Phosphoproteomics
- Protein phosphorylation
ASJC Scopus subject areas
- Biophysics
- Biochemistry