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

Document Type

Journal Article


R S C Publications


Faculty of Health, Engineering and Science


School of Medical Sciences/Centre of Excellence for Alzheimer's Disease Research and Care




This article was originally published as: Bharadwaj, P. , Head, R., Martins, R. N., Raussens, V., Sarroukh, R., Jegasothy, H., Waddington, L., & Bennett, L. (2013). Modulation of amyloid-β 1-42 structure and toxicity by proline-rich whey peptides. Food and Function, 4(1), 92-103. Original article available here


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 (Aβ42) 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 β-sheet and specifically, anti-parallel β-sheet structures by wPRP was demonstrated by ATR-FTIR spectroscopy, where evidence for capacity of wPRP to dissociate pre-existing β-sheet structures in Aβ42 was also apparent. Suppression of anti-parallel β-sheets of oligomeric Aβ42 was associated with rescue of yeast and SH-SY5Y neuronal cells providing important evidence for the association between anti-parallel β-sheet structure and oligomer toxicity. It was proposed that the interaction of wPRP with Aβ42 interfered with the anti-parallel folding pathway of oligomeric Aβ42 and ultimately produced 'off-pathway' structures of lowered total β-sheet content, with attenuated cellular toxicity.