Aberrant protein phosphorylation in Alzheimer disease brain disturbs pro-survival and cell death pathways
Autor: | Eugenio Barone, D A Butterfield, F. Di Domenico, Marzia Perluigi |
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Rok vydání: | 2016 |
Předmět: |
p53
0301 basic medicine Cell Survival Phosphatase Protein tyrosine phosphatase Biology Proteomics Alzheimer disease insulin protein phosphorylation proteomics molecular medicine molecular biology 03 medical and health sciences 0302 clinical medicine Alzheimer Disease medicine Animals Humans Insulin Protein phosphorylation Phosphorylation Molecular Biology Amyloid beta-Peptides Cell Death Kinase Brain medicine.disease Cell biology 030104 developmental biology Molecular Medicine Alzheimer's disease Signal transduction Tumor Suppressor Protein p53 Protein Processing Post-Translational 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | Biochimica et biophysica acta. 1862(10) |
ISSN: | 0006-3002 |
Popis: | Protein phosphorylation of serine, threonine, and tyrosine residues is one of the most prevalent post-translational modifications fundamental in mediating diverse cellular functions in living cells. Aberrant protein phosphorylation is currently recognized as a critical step in the pathogenesis and progression of Alzheimer disease (AD). Changes in the pattern of protein phosphorylation of different brain regions are suggested to promote AD transition from a presymptomatic to a symptomatic state in response to accumulating amyloid β-peptide (Aβ). Several experimental approaches have been utilized to profile alteration of protein phosphorylation in the brain, including proteomics. Among central pathways regulated by kinases/phosphatases those involved in the activation/inhibition of both pro survival and cell death pathways play a central role in AD pathology. We discuss in detail how aberrant phosphorylation could contribute to dysregulate p53 activity and insulin-mediated signaling. Taken together these results highlight that targeted therapeutic intervention, which can restore phosphorylation homeostasis, either acting on kinases and phosphatases, conceivably may prove to be beneficial to prevent or slow the development and progression of AD. |
Databáze: | OpenAIRE |
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