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

Food Funct. 2013 Jan;4(1):92-103. doi: 10.1039/c2fo30111c. Epub 2012 Sep 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / toxicity*
  • Blotting, Western
  • Candida glabrata / drug effects
  • Cell Line, Tumor
  • Cell Survival
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Microscopy, Electron, Transmission
  • Milk Proteins / chemistry
  • Milk Proteins / pharmacology*
  • Neurons / drug effects
  • Proline / chemistry*
  • Protein Binding
  • Protein Conformation
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Amyloid beta-Peptides
  • Milk Proteins
  • whey acidic proteins
  • Proline