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.
Copyright 2010 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Aminoacetonitrile / analogs & derivatives
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Aminoacetonitrile / pharmacology
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Amyloid beta-Peptides*
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Animals
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Brain-Derived Neurotrophic Factor / genetics
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Brain-Derived Neurotrophic Factor / metabolism
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Disease Models, Animal
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Enzyme Inhibitors / pharmacology
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Exploratory Behavior / drug effects
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Gene Expression Regulation / drug effects
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Hippocampus / drug effects
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Hippocampus / metabolism
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Isoleucine / administration & dosage
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Leucine / administration & dosage
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Male
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Memory Disorders / chemically induced*
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Memory Disorders / pathology
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Memory Disorders / prevention & control*
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Mice
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Mice, Inbred ICR
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / metabolism
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Oligopeptides / administration & dosage*
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Peptide Fragments*
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Phosphorylation / drug effects
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Recognition, Psychology / drug effects
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Time Factors
Substances
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Amyloid beta-Peptides
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Brain-Derived Neurotrophic Factor
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Enzyme Inhibitors
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Oligopeptides
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Peptide Fragments
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SL 327
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amyloid beta-protein (25-35)
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Isoleucine
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Aminoacetonitrile
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Nitric Oxide Synthase Type II
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Extracellular Signal-Regulated MAP Kinases
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Leucine