Short-chain peptides derived from various protein sources have been shown to exhibit diverse bio-modulatory and health-promoting effects in animal experiments and human trials. We recently reported that the oral administration of the Tyr-Trp (YW) dipeptide to mice markedly enhances noradrenaline metabolism in the brain and ameliorates the working-memory deficits induced by the β-amyloid 25-35 peptide (Aβ25-35). In the current study, we performed multiple bioinformatics analyses of microarray data from Aβ25-35/YW-treated brains to determine the mechanism underlying the action of YW in the brain and to infer the molecular mechanisms and networks involved in the protective effect of YW in the brain. We found that YW not only reversed inflammation-related responses but also activated various molecular networks involving a transcriptional regulatory system, which is mediated by the CREB binding protein (CBP), EGR-family proteins, ELK1, and PPAR, and the calcium-signaling pathway, oxidative stress tolerance, and an enzyme involved in de novo l-serine synthesis in brains treated with Aβ25-35. This study revealed that YW has a neuroprotective effect against Aβ25-35 neuropathy, suggesting that YW is a new functional-food-material peptide.
Keywords: Alzheimer’s disease; Phgdh; Tyr–Trp; food peptide; working-memory deficits.