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

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dc.contributor.authorChacon, Marcelo A.
dc.contributor.authorVarela-Nallar, Lorena
dc.contributor.authorInestrosa, Nibaldo C.
dc.date.accessioned2025-01-21T01:04:59Z
dc.date.available2025-01-21T01:04:59Z
dc.date.issued2008
dc.description.abstractThe activation of the canonical Writ signaling pathway protects hippocampal neurons against the toxicity of Alzheimer's amyloid-beta-peptide (A beta), however, the role played by the Writ receptors Frizzleds, has not been studied. We report here that Frizzled-1 mediates the activation of the canonical Wnt/beta-catenin pathway by Wnt3a in PC 12 cells. In addition, the protective effect of Wnt3a against the toxicity of A beta oligomers was modulated by Frizzled-1 expression levels in both PC 12 cells and hippocampal neurons. Over-expression of Frizzled-1 significantly increased cell survival induced by Wnt3a and diminished caspase-3 activation, while knocking-clown Frizzled-1 expression by antisense oligonucleotides decreased the Wnt3a protection. Over-expression of wild-type beta-catenin, but not a transcriptionally inactive mutated version, prevented the toxicity of A suggesting that the transcription of Writ target genes may be involved in these events. This was confirmed by co-transfecting both Frizzled-1 and the inactive form of beta-catenin, which does not elicited protection levels similar to those showed with endogenous beta-catenin. Our results indicate that Wnt3a protects from A beta-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.
dc.fuente.origenWOS
dc.identifier.doi10.1002/jcp.21497
dc.identifier.eissn1097-4652
dc.identifier.issn0021-9541
dc.identifier.urihttps://doi.org/10.1002/jcp.21497
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95768
dc.identifier.wosidWOS:000258899900023
dc.issue.numero1
dc.language.isoen
dc.pagina.final227
dc.pagina.inicio215
dc.revistaJournal of cellular physiology
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleFrizzled-1 is involved in the neuroprotective effect of Wnt3a against aβ oligomers
dc.typeartículo
dc.volumen217
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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