Andrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3 beta: autoregulation of GSK-3 beta in vivo

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dc.catalogadoraba
dc.contributor.authorTapia Rojas, C.
dc.contributor.authorSchüller, Andreas
dc.contributor.authorLindsay, C. B.
dc.contributor.authorUreta, R. C.
dc.contributor.authorMejias Reyes, C.
dc.contributor.authorHancke, J.
dc.contributor.authorMelo Ledermann, Francisco Javier
dc.contributor.authorInestrosa Cantín, Nibaldo
dc.date.accessioned2025-02-05T19:18:09Z
dc.date.available2025-02-05T19:18:09Z
dc.date.issued2015
dc.description.abstractWnt/β-catenin signalling is an important pathway that regulates multiple biological processes, including cell adhesion and determination of cell fate during animal development; in the adult nervous system it regulates the structure and function of synapses. Wnt-signalling dysfunction is associated with several neurodegenerative diseases such as schizophrenia and Alzheimer's disease. The use of natural compounds is an interesting strategy in the search for drugs with the therapeutic potential to activate this signalling pathway. In the present study, we report that andrographolide (ANDRO), a component of Andrographis paniculata, is a potent activator of Wnt signalling. Our results indicate that ANDRO activates this pathway, inducing the transcription of Wnt target genes by a mechanism that bypasses Wnt ligand binding to its receptor. In vitro kinase assays demonstrate that ANDRO inhibits glycogen synthase kinase (GSK)-3β by a non-ATP-competitive, substrate-competitive mode of action. In silico analyses suggest that ANDRO interacts with the substrate-binding site of GSK-3β. Finally, we demonstrated that the increase seen in the levels of GSK-3β phosphorylated at Ser9 is the result of an autoregulatory mechanism of the kinase in vivo, although not through activation of protein phosphatase type 1. Our results suggest that ANDRO could be used as a potential therapeutic drug for disorders caused by Wnt-signalling dysfunction such as neurodegenerative diseases.
dc.fuente.origenSIPA
dc.identifier.doi10.1042/BJ20140207
dc.identifier.eissn1470-8728
dc.identifier.issn0264-6021
dc.identifier.urihttps://doi.org/10.1042/BJ20140207
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/102156
dc.identifier.wosidWOS:000351686800020
dc.information.autorucFacultad de Ciencias Biológicas; Schüller, Andreas; 0000-0002-4443-4279; 207692
dc.information.autorucFacultad de Ciencias Biológicas; Melo Ledermann, Francisco Javier; 0000-0002-0424-5991; 82342
dc.information.autorucFacultad de Ciencias Biológicas; Inestrosa Cantín, Nibaldo; S/I; 99331
dc.issue.numero2
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final430
dc.pagina.inicio415
dc.revistaBIOCHEMICAL JOURNAL
dc.rightsacceso restringido
dc.subjectAndrographolide
dc.subjectGSK-3β
dc.subjectWnt/β-catenin
dc.subjectWnt signalling
dc.subjectWnt target genes
dc.subject.ddc570
dc.subject.deweyBiologíaes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleAndrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3 beta: autoregulation of GSK-3 beta in vivo
dc.typeartículo
dc.volumen466
sipa.codpersvinculados207692
sipa.codpersvinculados82342
sipa.codpersvinculados99331
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