Frizzled-1 is involved in the neuroprotective effect of Wnt3a against Aβ oligomers
Article first published online: 2 JUN 2008
Copyright © 2008 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 217, Issue 1, pages 215–227, October 2008
How to Cite
Chacón, M. A., Varela-Nallar, L. and Inestrosa, N. C. (2008), Frizzled-1 is involved in the neuroprotective effect of Wnt3a against Aβ oligomers. J. Cell. Physiol., 217: 215–227. doi: 10.1002/jcp.21497
- Issue published online: 21 JUL 2008
- Article first published online: 2 JUN 2008
- Manuscript Accepted: 16 APR 2008
- Manuscript Received: 5 MAR 2008
- FONDAP. Grant Number: 13980001
- FONDECYT. Grant Number: 3070017
- CONICYT. Grant Numbers: 102025, 4040214
The activation of the canonical Wnt signaling pathway protects hippocampal neurons against the toxicity of Alzheimer's amyloid-β-peptide (Aβ), however, the role played by the Wnt receptors Frizzleds, has not been studied. We report here that Frizzled-1 mediates the activation of the canonical Wnt/β-catenin pathway by Wnt3a in PC12 cells. In addition, the protective effect of Wnt3a against the toxicity of Aβ oligomers was modulated by Frizzled-1 expression levels in both PC12 cells and hippocampal neurons. Over-expression of Frizzled-1 significantly increased cell survival induced by Wnt3a and diminished caspase-3 activation, while knocking-down Frizzled-1 expression by antisense oligonucleotides decreased the Wnt3a protection. Over-expression of wild-type β-catenin, but not a transcriptionally inactive mutated version, prevented the toxicity of Aβ suggesting that the transcription of Wnt target genes may be involved in these events. This was confirmed by co-transfecting both Frizzled-1 and the inactive form of β-catenin, which does not elicited protection levels similar to those showed with endogenous β-catenin. Our results indicate that Wnt3a protects from Aβ-oligomers toxicity by activating the canonical Wnt signaling pathway through the Frizzled-1 receptor, suggesting a therapeutic potential for this signaling pathway in the treatment of Alzheimer's disease. J. Cell. Physiol. 217: 215–227, 2008. © 2008 Wiley-Liss, Inc.