CSIRO Preventative Health Flagship, Material Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052, Australia.
Food Funct. 2013 Jan;4(1):92-103. doi: 10.1039/c2fo30111c. Epub 2012 Sep 27.
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.
一种从牛乳蛋白中提取的富含脯氨酸的多肽产品，富含脯氨酸（乳富含脯氨酸多肽，wPRP）和几种疏水性氨基酸，被证明可以调节人淀粉样β肽 1-42（Aβ42）的折叠途径形成寡聚物。wPRP 对 Ab42 的 ThT 结合的浓度依赖性变化表明其对寡聚化的抑制作用，这得到了透射电子显微镜的支持。ATR-FTIR 光谱表明，wPRP 抑制β-折叠，特别是抑制反平行β-折叠结构，并且明显证明 wPRP 具有在 Aβ42 中解离预先存在的β-折叠结构的能力。寡聚 Aβ42 的反平行 β-折叠的抑制与酵母和 SH-SY5Y 神经元细胞的拯救有关，这为反平行 β-折叠结构与寡聚物毒性之间的关联提供了重要证据。据推测，wPRP 与 Aβ42 的相互作用干扰了寡聚 Aβ42 的反平行折叠途径，最终产生了总β-折叠含量降低的“偏离途径”结构，细胞毒性减弱。
