title: Quantitative proteomics analysis of phosphorylated proteins in the hippocampus of Alzheimer's disease subjects.
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.
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Domenico
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.forename: Eugenio
authors.initials: E
authors.lastname: Barone
authors.forename: Marzia
authors.initials: M
authors.lastname: Perluigi
authors.forename: Chiara
authors.initials: C
authors.lastname: Cini
authors.forename: Cesare
authors.initials: C
authors.lastname: Mancuso
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.forename: William M
authors.initials: WM
authors.lastname: Pierce
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000502:physiology; D016874:Neurofibrillary Tangles / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D015398:Signal Transduction / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016875:tau Proteins