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

Prashant Bharadwaj, Richard Head, Ralph Martins, Vincent Raussens, Rabia Sarroukh, Hema Jegasothy, Lynne Waddington, Louise Bennett*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)92-103
Number of pages12
JournalFood and Function
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 2013
Externally publishedYes

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