title: Modulation of amyloid-β 1-42 structure and toxicity by proline-rich whey peptides.
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.
authors.affiliation: CSIRO Preventative Health Flagship, Material Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Prashant
authors.initials: P
authors.lastname: Bharadwaj
authors.forename: Richard
authors.initials: R
authors.lastname: Head
authors.forename: Ralph
authors.initials: R
authors.lastname: Martins
authors.forename: Vincent
authors.initials: V
authors.lastname: Raussens
authors.forename: Rabia
authors.initials: R
authors.lastname: Sarroukh
authors.forename: Hema
authors.initials: H
authors.lastname: Jegasothy
authors.forename: Lynne
authors.initials: L
authors.lastname: Waddington
authors.forename: Louise
authors.initials: L
authors.lastname: Bennett
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity*; D015153:Blotting, Western; D041221:Candida glabrata / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008894:Milk Proteins / Q000737:chemistry / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D011392:Proline / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D016229:Amyloid beta-Peptides; D008894:Milk Proteins; C024471:whey acidic proteins; D011392:Proline