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.

Abstract

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.

• Authors: Tursun Alkam, Atsumi Nitta, Yoko Furukawa-Hibi, Minae Niwa, Hiroyuku Mizoguchi, Kiyofumi Yamada, Toshitaka Nabeshima
• Journal: Behavioural brain research (Behav Brain Res) Vol. 210 Issue 2 Pg. 184-90 (Jul 11 2010) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 20171988 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Brain-Derived Neurotrophic Factor
• Enzyme Inhibitors
• Oligopeptides
• Peptide Fragments
• SL 327
• amyloid beta-protein (25-35)
• Isoleucine
• Aminoacetonitrile
• Nitric Oxide Synthase Type II
• Extracellular Signal-Regulated MAP Kinases
• Leucine

Topics

• Administration, Oral
• Aminoacetonitrile (analogs & derivatives, pharmacology)
• Amyloid beta-Peptides
• Animals
• Brain-Derived Neurotrophic Factor (genetics, metabolism)
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Exploratory Behavior (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Gene Expression Regulation (drug effects)
• Hippocampus (drug effects, metabolism)
• Isoleucine (administration & dosage)
• Leucine (administration & dosage)
• Male
• Memory Disorders (chemically induced, pathology, prevention & control)
• Mice
• Mice, Inbred ICR
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Oligopeptides (administration & dosage)
• Peptide Fragments
• Phosphorylation (drug effects)
• Recognition, Psychology (drug effects)
• Time Factors