Browsing by Author "Tapia Rojas, C."

Now showing 1 - 4 of 4
  • No Thumbnail Available
    Item
    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
    (2015) Tapia Rojas, C.; Schüller, Andreas; Lindsay, C. B.; Ureta, R. C.; Mejias Reyes, C.; Hancke, J.; Melo Ledermann, Francisco Javier; Inestrosa Cantín, Nibaldo
    Wnt/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.
  • Thumbnail Image
    Item
    Hormetic-Like Effects of L-Homocysteine on Synaptic Structure, Function, and A beta Aggregation
    (2020) Montecinos Oliva, Carla; Arrazola Tello, Macarena Soledad; Jara, C.; Tapia Rojas, C.; Inestrosa Cantín, Nibaldo
  • Thumbnail Image
    Item
    Palmitic acid reduces the autophagic flux in hypothalamic neurons by impairing autophagosome-lysosome fusion and endolysosomal dynamics
    (2020) Hernández Cáceres, María Paz; Cereceda, K.; Hernández, S.; Li, Y.; Rivera Reyes, Patricia Ximena; Toledo Valenzuela, Lilian Alejandra; Cifuentes Araneda, Flavia Dominique; Pérez Leighton, Claudio; Bertocchi, Cristina; Morselli, Eugenia; Narro, C.; Silva, P.; Avalos, Y.; Jara, C.; Burgos, P.; Lagos, P.; Clegg, D. J.; Criollo, A.; Tapia Rojas, C.; Burgos, P. V.
  • Thumbnail Image
    Item
    Wnt Signaling Pathway Dysregulation in the Aging Brain : Lessons From theOctodon degus
    (2020) Inestrosa Cantín, Nibaldo; Tapia Rojas, C.; Lindsay, C. B.; Zolezzi, J. M.