Protein kinase C inhibits amyloid β-peptide neurotoxicity by acting on members of the Wnt pathway

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dc.contributor.authorGarrido, JL
dc.contributor.authorGodoy, J
dc.contributor.authorAlvarez, A
dc.contributor.authorBronfman, M
dc.contributor.authorInestrosa, NC
dc.date.accessioned2025-01-21T01:10:28Z
dc.date.available2025-01-21T01:10:28Z
dc.date.issued2002
dc.description.abstractCurrent evidence supports the notion that the amyloid beta-peptide (Abeta) plays a major role in the neurotoxicity observed in the brain in Alzheimer's disease. However, the signal transduction mechanisms involved still remain unknown. In the present work, we analyzed the effect of protein kinase C (PKC) on some members of the Writ signaling pathway and its implications for Abeta neurotoxicity. Activation of PKC by phorbol 12-myristate 13-acetate protected rat hippocampal neurons from A(3 toxicity. This effect was accomplished by inhibition of glycogen synthase kinase-3beta (GSK-3beta) activity, which led to the accumulation of cytoplasmic beta-catenin and transcriptional activation via beta-catenin/T-cell factor/lymphoid enhancer factor-1 (TCF/LEF-1) of Writ target genes, which in the present study were engrailed-1 (en-1) and cyclin D1 (cycD1). In contrast, inhibition of Ca2+-dependent PKC isoforms activated GSK-3beta and offered no protection from Abeta neurotoxicity. Wnt-3a and lithium salts, classical activators of the Writ pathway, mimicked PKC activation. Our results suggest that regulation of members of the Writ signaling pathway by Ca2+-dependent PKC isoforms may be important in controlling the neurotoxic process induced by Abeta.
dc.fuente.origenWOS
dc.identifier.doi10.1096/fj.02-0327fje
dc.identifier.eissn1530-6860
dc.identifier.issn0892-6638
dc.identifier.urihttps://doi.org/10.1096/fj.02-0327fje
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96688
dc.identifier.wosidWOS:000179167600001
dc.issue.numero12
dc.language.isoen
dc.pagina.final+
dc.pagina.inicio1982
dc.revistaFaseb journal
dc.rightsacceso restringido
dc.subjectA beta neurotoxicity
dc.subjectPKC
dc.subjectWnt signaling
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleProtein kinase C inhibits amyloid β-peptide neurotoxicity by acting on members of the Wnt pathway
dc.typeartículo
dc.volumen16
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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