Abstract
The aim of this study was to evaluate whether the direct activation of the Wnt signaling pathway by its endogenous Wnt-3a ligand prevents the toxic effects induced by amyloid-beta-peptide (Abeta) in rat hippocampal neurons. We report herein that the Wnt-3a ligand was indeed able to overcome toxic effects induced by Abeta in hippocampal neurons, including a neuronal impairment on cell survival, an increase in glycogen synthase kinase-3beta (GSK-3beta) and tau phosphorylation, a decrease in cytoplasmic beta-catenin and a decrease in the expression of the Wnt target gene engrailed-1. We further demonstrate that Wnt-3a protects hippocampal neurons from apoptosis induced by Abeta. Our results support the hypothesis that a loss of function of Wnt signaling may play a role in the progression of neurodegenerative diseases such as Alzheimer's disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / genetics
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Alzheimer Disease / metabolism
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Alzheimer Disease / physiopathology
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Amyloid beta-Peptides / antagonists & inhibitors*
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Amyloid beta-Peptides / metabolism
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Amyloid beta-Peptides / toxicity
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology
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Cell Survival / drug effects
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Cell Survival / physiology
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Cells, Cultured
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Culture Media, Conditioned / pharmacology
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Cytoskeletal Proteins / drug effects
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Cytoskeletal Proteins / metabolism
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Glycogen Synthase Kinase 3 / drug effects
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Hippocampus / cytology
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Hippocampus / embryology
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Homeodomain Proteins / drug effects
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Homeodomain Proteins / metabolism
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Ligands
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Nerve Degeneration / drug therapy
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Nerve Degeneration / metabolism*
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Nerve Degeneration / prevention & control
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Nerve Tissue Proteins / drug effects
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Nerve Tissue Proteins / metabolism
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Neurons / drug effects
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Neurons / metabolism*
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Neurons / pathology
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Neuroprotective Agents / metabolism*
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Neuroprotective Agents / pharmacology
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Oxidative Stress / drug effects
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Oxidative Stress / physiology
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Phosphorylation / drug effects
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Proteins / agonists
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Proteins / metabolism*
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Proteins / pharmacology
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Rats
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Rats, Sprague-Dawley
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Trans-Activators / drug effects
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Trans-Activators / metabolism
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Up-Regulation / drug effects
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Up-Regulation / physiology
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Wnt Proteins
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Wnt3 Protein
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beta Catenin
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tau Proteins / drug effects
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tau Proteins / metabolism
Substances
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Amyloid beta-Peptides
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Ctnnb1 protein, rat
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Culture Media, Conditioned
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Cytoskeletal Proteins
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Homeodomain Proteins
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Ligands
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Nerve Tissue Proteins
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Neuroprotective Agents
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Proteins
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Trans-Activators
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Wnt Proteins
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Wnt3 Protein
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beta Catenin
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engrailed 2 protein
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tau Proteins
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, rat
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Glycogen Synthase Kinase 3