Abstract
Current understanding of amyloid-β (Aβ) metabolism and toxicity provides an extensive list of potential targets for developing drugs for treating Alzheimer's disease. We took two independent approaches, including synaptic-plasticity-based analysis and behavioral screening of synthetic compounds, for identifying single compounds that are capable of rescuing the Aβ-induced memory loss in both transgenic fruit fly and transgenic mouse models. Two clinically available drugs and three synthetic compounds not only showed positive effects in behavioral tests but also antagonized the Aβ oligomers-induced activation of the epidermal growth factor receptor (EGFR). Such surprising converging outcomes from two parallel approaches lead us to conclude that EGFR is a preferred target for treating Aβ-induced memory loss.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyloid beta-Peptides / genetics
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Amyloid beta-Peptides / metabolism*
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Animals
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Animals, Genetically Modified
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Blotting, Western
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COS Cells
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Chlorocebus aethiops
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Drosophila
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Drosophila Proteins / antagonists & inhibitors
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Drosophila Proteins / metabolism
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Drug Evaluation, Preclinical / methods
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / metabolism
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Erlotinib Hydrochloride
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Gefitinib
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Humans
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Maze Learning / drug effects
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Memantine / pharmacology
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Memory / drug effects
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Memory Disorders / genetics
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Memory Disorders / metabolism
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Memory Disorders / prevention & control*
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Mice
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Mice, Transgenic
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Molecular Structure
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Quinazolines / pharmacology
Substances
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Amyloid beta-Peptides
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Drosophila Proteins
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Peptide Fragments
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Protein Kinase Inhibitors
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Quinazolines
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amyloid beta-protein (1-42)
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Erlotinib Hydrochloride
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ErbB Receptors
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Gefitinib
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Memantine