Frizzled-1 is involved in the neuroprotective effect of Wnt3a against a beta oligomers

Chacón MA; Varela-Nallar, L; Inestrosa, NC

Abstract

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. © 2008 Wiley-Liss, Inc.

Más información

Título según WOS: Frizzled-1 is involved in the neuroprotective effect of Wnt3a against a beta oligomers
Título según SCOPUS: Frizzled-1 is involved in the neuroprotective effect of Wnt3a against Aß oligomers
Título de la Revista: JOURNAL OF CELLULAR PHYSIOLOGY
Volumen: 217
Número: 1
Editorial: WILEY-BLACKWELL
Fecha de publicación: 2008
Página de inicio: 215
Página final: 227
Idioma: English
URL: http://doi.wiley.com/10.1002/jcp.21497
DOI:

10.1002/jcp.21497

Notas: ISI, SCOPUS