Modulation of amyloid-β 1-42 structure and toxicity by proline-rich whey peptides
Document Type
Journal Article
Keywords
Amyloid betas, ATR-FT-IR spectroscopy, Cellular toxicities, Concentration-dependent, Folding pathway, Hydrophobic amino acids, Neuronal cell, Peptide products, Sheet structure, Whey proteins, Fourier transform infrared spectroscopy, Glycoproteins, Oligomerization, Oligomers, Peptides, Toxicity, Transmission electron microscopy, Amino acids, Bovinae, amyloid beta protein, milk protein, proline, whey acidic proteins, article, Candida glabrata, cell survival, chemistry, drug effect, human, infrared spectroscopy, nerve cell, polyacrylamide gel electrophoresis, protein binding, protein conformation, transmission electron microscopy, tumor cell line, Western blotting, Amyloid beta-Peptides, Blotting, Western, Candida glabrata, Cell Line, Tumor, Cell Survival, Electrophoresis, Polyacrylamide Gel, Humans, Microscopy, Electron, Transmission, Milk Proteins, Neurons, Proline, Protein Binding, Protein Conformation, Spectroscopy, Fourier Transform Infrared
Publisher
R S C Publications
Faculty
Faculty of Health, Engineering and Science
School
School of Medical Sciences / Centre of Excellence for Alzheimer's Disease Research and Care
RAS ID
16927
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.
Comments
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. Available here