Aberrant protein phosphorylation in Alzheimer disease brain disturbs pro-survival and cell death pathways

M. Perluigi, E. Barone, F. Di Domenico, D. A. Butterfield

Research output: Contribution to journalReview articlepeer-review

55 Scopus citations

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 languageEnglish
Pages (from-to)1871-1882
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1862
Issue number10
DOIs
StatePublished - Oct 1 2016

Bibliographical note

Funding Information:
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.

Publisher Copyright:
© 2016 Elsevier B.V.

Keywords

  • Alzheimer disease
  • Insulin
  • Protein phosphorylation
  • Proteomics
  • p53

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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