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

Marcelo A. Chacón, Lorena Varela-Nallar, Nibaldo C. Inestrosa

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

81 Citas (Scopus)

Resumen

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.

Idioma originalInglés
Páginas (desde-hasta)215-227
Número de páginas13
PublicaciónJournal of Cellular Physiology
Volumen217
N.º1
DOI
EstadoPublicada - oct. 2008

Áreas temáticas de ASJC Scopus

  • Fisiología
  • Bioquímica clínica
  • Biología celular

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