Abstract
The peptide amphiphile (PA) with a laminin epitope IKVAV (IKVAV-PA) can be trigged into three-dimensional nanostructures in vivo. Application of IKVAV-PA to the injured spinal cord resulted in significant functional improvement in rodents with remarkable axonal regeneration at the lesion site. Here we showed that injection of IKVAV-PA into the hippocampus of a transgenic (Tg) mice model of Alzheimer's disease (AD) significantly improved cognitive impairment, accompanied by an enhanced neurogenesis in the hippocampus. Further examination demonstrated that IKVAV-PA injections also significantly reduced the levels of soluble Aβ1-40, Aβ1-42, and amyloid-beta (Aβ) plaques in these brains. Our data suggest that IKVAV-PA may serve as a potential therapeutic intervention for the learning and memory losses in AD.
Keywords:
Alzheimer's disease; Amyloid-beta; Cognition; Neurogenesis; Peptide amphiphile.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / drug therapy*
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Alzheimer Disease / pathology
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Alzheimer Disease / psychology
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Amyloid beta-Peptides / metabolism
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Animals
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Brain / drug effects*
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Brain / metabolism
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Brain / pathology
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Cell Differentiation
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Cognition Disorders / drug therapy*
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Cognition Disorders / psychology
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Hippocampus / drug effects
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Hippocampus / pathology
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Laminin / therapeutic use*
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MAP Kinase Signaling System
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Maze Learning / drug effects
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Memory / drug effects
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Mice
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Mice, Transgenic
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Nanofibers / therapeutic use*
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Neural Stem Cells / drug effects
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Neural Stem Cells / pathology
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Neurogenesis
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Neurons / drug effects
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Neurons / pathology
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Peptide Fragments / metabolism
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Peptide Fragments / therapeutic use*
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Plaque, Amyloid / pathology
Substances
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Amyloid beta-Peptides
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Laminin
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Peptide Fragments
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amyloid beta-protein (1-40)
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amyloid beta-protein (1-42)
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isoleucyl-lysyl-valyl-alanyl-valine
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3