Abstract
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.
Original language | English |
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Pages (from-to) | 1871-1882 |
Number of pages | 12 |
Journal | Biochimica et Biophysica Acta - Molecular Basis of Disease |
Volume | 1862 |
Issue number | 10 |
DOIs | |
State | Published - Oct 1 2016 |
Bibliographical note
Publisher Copyright:© 2016 Elsevier B.V.
Funding
All authors state that they have no conflicts of interest. This work was partially supported by Fondi di Ateneo Sapienza to M.P. and F.D.D. and funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007–2013) under REA grant agreement no. 624341 to E.B. and M.P.
Funders | Funder number |
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FP7/2007 | |
Fondi di Ateneo Sapienza | |
Marie Curie | |
Research Executive Agency | 624341 |
Seventh Framework Programme |
Keywords
- Alzheimer disease
- Insulin
- Protein phosphorylation
- Proteomics
- p53
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology