Wnt-3a overcomes β-amyloid toxicity in rat hippocampal neurons

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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-β-peptide (Aβ) in rat hippocampal neurons. We report herein that the Wnt-3a ligand was indeed able to overcome toxic effects induced by Aβ in hippocampal neurons, including a neuronal impairment on cell survival, an increase in glycogen synthase kinase-3β (GSK-3β) and tau phosphorylation, a decrease in cytoplasmic β-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 Aβ. 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.

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