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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 (Ab42) into oligomers. Concentrationdependent changes in ThT-binding to Ab42 by wPRP indicated suppression of oligomerisation, that was supported by Transmission Electron Microscopy. Suppression of b-sheet and specifically, antiparallel b-sheet structures by wPRP was demonstrated by ATR-FTIR spectroscopy, where evidence for capacity of wPRP to dissociate pre-existing b-sheet structures in Ab42 was also apparent. Suppression of anti-parallel b-sheets of oligomeric Ab42 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 Ab42 interfered with the antiparallel folding pathway of oligomeric Ab42 and ultimately produced 'off-pathway' structures of lowered total b-sheet content, with attenuated cellular toxicity. IntroductionIn 2010, cases of dementia including Alzheimer's disease (AD) affected 35.6 million people worldwide with predicted increase of 65.7 million to 115.4 million from 2030 to 2050, according to Alzheimer's Disease International, the worldwide federation of Alzheimer's Associations. The substantial projected social and economic burden of AD world-wide has driven the need for evaluation of the costs of the illness, the cost-effectiveness of interventions and ultimately, the implementation of public policies and services.1 Disease-modifying therapies remain a high priority for development and use in AD care, however the current absence of effective disease-modifying therapies reflects the significant challenge posed by this goal. Furthermore, as preventative measures are likely to be most effective in presymptomatic stages of disease, diet and lifestyle interventions are favoured at this stage. Of relevance to this study is the precedent set by the proline-rich peptide extract prepared from ovine colostrums known as 'Colostrinin' 2 for which anti-fibril and other neuroprotective bioactivities have been extensively reported.Amyloid beta (Ab) is a 40 or 42 amino acid cleavage product of Amyloid Precursor Protein (APP) produced in low levels in the normal ageing brain. It is the major component of senile extracellular plaques in the brain of AD patients and increased levels of Ab42 and its self-aggregation in the brain are key events thought to be responsible for the progressive cognitive decline associated with AD.3 In addition to the heterogeneity and toxic variability of extra-cellular amyloid structures, 4 disease progression has also been attributed to the retention of intracellular Ab42.5 Amyloid fibrils comprise highly ordered, cross-bsheet arrays that elongate into long fibrils and aggregate as tangled plaques. Oligomeric Ab42 represents a low mass, soluble form of Ab42 produced by an ear...

Mild heating coupled with fermentation: a novel approach for increasing sulforaphane yield in broccoli.

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