Protein array based interactome analysis of amyloid-β indicates an inhibition of protein translation.
Oligomeric amyloid-β is currently of interest in amyloid-β mediated toxicity and the pathogenesis of Alzheimer's 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.
Institute for Plant Genomics, Human Biotechnology, Bioenergy Bay-Gen and Szeged, Hungary. virok@baygen.hu
Dezso P
DP
Virok
Dóra
D
Simon
Zsolt
Z
Bozsó
Róbert
R
Rajkó
Zsolt
Z
Datki
Éva
É
Bálint
Viktor
V
Szegedi
Tamás
T
Janáky
Botond
B
Penke
Lívia
L
Fülöp
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D006801:Humans; D040081:Protein Array Analysis / Q000379:methods*; D011485:Protein Binding; D014176:Protein Biosynthesis; D025941:Protein Interaction Mapping / Q000379:methods*; D055503:Protein Multimerization; D020543:Proteome / Q000032:analysis; D051381:Rats; D012270:Ribosomes / Q000378:metabolism
D016229:Amyloid beta-Peptides; D020543:Proteome