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-?-peptide (A?) in rat hippocampal neurons. We report herein that the Wnt-3a ligand was indeed able to overcome toxic effects induced by A? in hippocampal neurons, including a neuronal impairment on cell survival, an increase in glycogen synthase kinase-3? (GSK-3?) and tau phosphorylation, a decrease in cytoplasmic ?-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 A?. 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. © 2004 Elsevier Inc. All rights reserved.