Modulation of amyloid-ß 1-42 structure and toxicity by proline-rich whey peptides

A proline-rich peptide product prepared from bovine whey protein that was enriched in several hydrophobic amino acids including proline (whey proline-rich peptide, wPRP) was shown to modulate the folding pathway of human amyloid beta peptide 1-42 (Aß42) into oligomers. Concentration-dependent change...

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Main Authors: Bharadwaj, Prashant, Head, R., Martins, R., Raussens, V., Sarroukh, R., Jegasothy, H., Waddington, L., Bennett, L.
Format: Journal Article
Published: 2013
Online Access:http://hdl.handle.net/20.500.11937/25238
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author Bharadwaj, Prashant
Head, R.
Martins, R.
Raussens, V.
Sarroukh, R.
Jegasothy, H.
Waddington, L.
Bennett, L.
author_facet Bharadwaj, Prashant
Head, R.
Martins, R.
Raussens, V.
Sarroukh, R.
Jegasothy, H.
Waddington, L.
Bennett, L.
author_sort Bharadwaj, Prashant
building Curtin Institutional Repository
collection Online Access
description A proline-rich peptide product prepared from bovine whey protein that was enriched in several hydrophobic amino acids including proline (whey proline-rich peptide, wPRP) was shown to modulate the folding pathway of human amyloid beta peptide 1-42 (Aß42) into oligomers. Concentration-dependent changes in ThT-binding to Ab42 by wPRP indicated suppression of oligomerisation, that was supported by Transmission Electron Microscopy. Suppression of ß-sheet and specifically, anti-parallel ß-sheet structures by wPRP was demonstrated by ATR-FTIR spectroscopy, where evidence for capacity of wPRP to dissociate pre-existing ß-sheet structures in Aß42 was also apparent. Suppression of anti-parallel ß-sheets of oligomeric Aß42 was associated with rescue of yeast and SH-SY5Y neuronal cells providing important evidence for the association between anti-parallel ß-sheet structure and oligomer toxicity. It was proposed that the interaction of wPRP with Aß42 interfered with the anti-parallel folding pathway of oligomeric Aß42 and ultimately produced 'off-pathway' structures of lowered total ß-sheet content, with attenuated cellular toxicity. © 2013 The Royal Society of Chemistry.
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spelling curtin-20.500.11937-252382018-03-29T09:08:51Z Modulation of amyloid-ß 1-42 structure and toxicity by proline-rich whey peptides Bharadwaj, Prashant Head, R. Martins, R. Raussens, V. Sarroukh, R. Jegasothy, H. Waddington, L. Bennett, L. A proline-rich peptide product prepared from bovine whey protein that was enriched in several hydrophobic amino acids including proline (whey proline-rich peptide, wPRP) was shown to modulate the folding pathway of human amyloid beta peptide 1-42 (Aß42) into oligomers. Concentration-dependent changes in ThT-binding to Ab42 by wPRP indicated suppression of oligomerisation, that was supported by Transmission Electron Microscopy. Suppression of ß-sheet and specifically, anti-parallel ß-sheet structures by wPRP was demonstrated by ATR-FTIR spectroscopy, where evidence for capacity of wPRP to dissociate pre-existing ß-sheet structures in Aß42 was also apparent. Suppression of anti-parallel ß-sheets of oligomeric Aß42 was associated with rescue of yeast and SH-SY5Y neuronal cells providing important evidence for the association between anti-parallel ß-sheet structure and oligomer toxicity. It was proposed that the interaction of wPRP with Aß42 interfered with the anti-parallel folding pathway of oligomeric Aß42 and ultimately produced 'off-pathway' structures of lowered total ß-sheet content, with attenuated cellular toxicity. © 2013 The Royal Society of Chemistry. 2013 Journal Article http://hdl.handle.net/20.500.11937/25238 10.1039/c2fo30111c restricted
spellingShingle Bharadwaj, Prashant
Head, R.
Martins, R.
Raussens, V.
Sarroukh, R.
Jegasothy, H.
Waddington, L.
Bennett, L.
Modulation of amyloid-ß 1-42 structure and toxicity by proline-rich whey peptides
title Modulation of amyloid-ß 1-42 structure and toxicity by proline-rich whey peptides
title_full Modulation of amyloid-ß 1-42 structure and toxicity by proline-rich whey peptides
title_fullStr Modulation of amyloid-ß 1-42 structure and toxicity by proline-rich whey peptides
title_full_unstemmed Modulation of amyloid-ß 1-42 structure and toxicity by proline-rich whey peptides
title_short Modulation of amyloid-ß 1-42 structure and toxicity by proline-rich whey peptides
title_sort modulation of amyloid-ß 1-42 structure and toxicity by proline-rich whey peptides
url http://hdl.handle.net/20.500.11937/25238