Oral supplementation with Leu-Ile, a hydrophobic dipeptide, prevents the impairment of memory induced by amyloid beta in mice via restraining the hyperphosphorylation of extracellular signal-regulated kinase

Restraining the toxic pathways of amyloid beta peptide (Aβ) by daily supplementation with dietary products has been shown effective in preventing cognitive decline. In this study, we examined the effects of the orally administered Leu-Ile, a hydrophobic dipeptide, on the neurotoxicity of Aβ25–35 in mice. Chronic daily treatment with Leu-Ile prevented the Aβ25–35-induced protein nitration and impairment of novel object recognition memory in mice. Protein nitration in the hippocampus induced by Aβ25–35 was associated with the hyperphosphorylation of extracellular signal-regulated kinase (ERK) which was found responsible for the over-expression of inducible nitric oxide synthase. Sub-chronic treatment with Leu-Ile prevented the Aβ25–35-induced hyperphosphorylation of ERK and protein nitration in the hippocampus. The results suggested that with the protective property against the neurotoxicity of Aβ25–35, Leu-Ile could be considered as a candidate for the dietary supplementation in the prevention of Aβ-related impairment of recognition memory.