Department of Neuropsychopharmacology & Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Behav Brain Res. 2010 Jul 11;210(2):184-90. doi: 10.1016/j.bbr.2010.02.028. Epub 2010 Feb 19.
Restraining the toxic pathways of amyloid beta peptide (Abeta) 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 Abeta(25-35) in mice. Chronic daily treatment with Leu-Ile prevented the Abeta(25-35)-induced protein nitration and impairment of novel object recognition memory in mice. Protein nitration in the hippocampus induced by Abeta(25-35) 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 Abeta(25-35)-induced hyperphosphorylation of ERK and protein nitration in the hippocampus. The results suggested that with the protective property against the neurotoxicity of Abeta(25-35), Leu-Ile could be considered as a candidate for the dietary supplementation in the prevention of Abeta-related impairment of recognition memory.
通过日常补充膳食产品来抑制淀粉样β肽（Abeta）的毒性途径已被证明可有效预防认知能力下降。在这项研究中，我们研究了经口给予疏水性二肽 Leu-Ile 对 Abeta(25-35)在小鼠中的神经毒性的影响。慢性每日给予 Leu-Ile 可预防 Abeta(25-35)诱导的小鼠蛋白硝化和新物体识别记忆障碍。Abeta(25-35)诱导的海马蛋白硝化与细胞外信号调节激酶（ERK）的过度磷酸化有关，ERK 过度磷酸化导致诱导型一氧化氮合酶的过度表达。亚慢性给予 Leu-Ile 可预防 Abeta(25-35)诱导的 ERK 过度磷酸化和海马蛋白硝化。结果表明，Leu-Ile 具有对抗 Abeta(25-35)神经毒性的保护作用，可考虑将其作为膳食补充剂预防 Abeta 相关认知记忆障碍的候选药物。
