Protein array based interactome analysis of amyloid-β indicates an inhibition of protein translation

D. Virók, Dóra Simon, Z. Bozsó, R. Rajkó, Zsolt Datki, Éva Bálint, Viktor Szegedi, T. Janáky, B. Penke, L. Fülöp

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Oligomeric amyloid-β is currently of interest in amyloid-β mediated toxicity and the pathogenesis of Alzheimers disease. Mapping the amyloid-β interaction partners could help to discover novel pathways in disease pathogenesis. To discover the amyloid-β interaction partners, we applied a protein array with more than 8100 unique recombinantly expressed human proteins. We identified 324 proteins as potential interactors of oligomeric amyloid-β. The Gene Ontology functional analysis of these proteins showed that oligomeric amyloid-β bound to multiple proteins with diverse functions both from extra and intracellular localizations. This undiscriminating binding phenotype indicates that multiple protein interactions mediate the toxicity of the oligomeric amyloid-β. The most highly impacted cellular system was the protein translation machinery. Oligomeric amyloid-β could bind to altogether 24 proteins involved in translation initiation and elongation. The binding of amyloid-β to purified rat hippocampal ribosomes validated the protein array results. More importantly, in vitro translation assays showed that the oligomeric amyloid-β had a concentration dependent inhibitory activity on translation. Our results indicate that the inhibited protein synthesis is one of the pathways that can be involved in the amyloid-beta induced neurotoxicity.

Original languageEnglish
Pages (from-to)1538-1547
Number of pages10
JournalJournal of Proteome Research
Volume10
Issue number4
DOIs
Publication statusPublished - Apr 1 2011

Fingerprint

Protein Array Analysis
Protein Biosynthesis
Amyloid
Proteins
Toxicity
Inhibition (Psychology)
Functional analysis
Gene Ontology
Ribosomes
Machinery
Ontology
Rats
Elongation
Assays
Alzheimer Disease
Genes

Keywords

  • Alzheimers
  • amyloid-β
  • interactome
  • oligomeric
  • protein array
  • protein chip
  • proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Protein array based interactome analysis of amyloid-β indicates an inhibition of protein translation. / Virók, D.; Simon, Dóra; Bozsó, Z.; Rajkó, R.; Datki, Zsolt; Bálint, Éva; Szegedi, Viktor; Janáky, T.; Penke, B.; Fülöp, L.

In: Journal of Proteome Research, Vol. 10, No. 4, 01.04.2011, p. 1538-1547.

Research output: Contribution to journalArticle

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