Modulation of amyloid-β 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 (A beta 42) 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 beta-sheet and specifically, anti-parallel beta-sheet structures by wPRP was demonstrated by ATR-FTIR spectroscopy, where evidence for capacity of wPRP to dissociate pre-existing beta-sheet structures in A beta 42 was also apparent. Suppression of anti-parallel beta-sheets of oligomeric A beta 42 was associated with rescue of yeast and SH-SY5Y neuronal cells providing important evidence for the association between anti-parallel b-sheet structure and oligomer toxicity. It was proposed that the interaction of wPRP with A beta 42 interfered with the anti-parallel folding pathway of oligomeric A beta 42 and ultimately produced 'off-pathway' structures of lowered total b-sheet content, with attenuated cellular toxicity.