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dc.creatorNavarro Garrido, Victoriaes
dc.creatorVitorica Ferrández, Francisco Javieres
dc.creatorFernández, Ana M.es
dc.creatorHervasa, Rubénes
dc.creatorGómez Gutiérrez, Patriciaes
dc.creatorVega, Migueles
dc.date.accessioned2019-06-27T18:02:06Z
dc.date.available2019-06-27T18:02:06Z
dc.date.issued2016
dc.identifier.citationNavarro Garrido, V., Vitorica Ferrández, F.J., Fernández, A.M., Hervasa, R., Gómez Gutiérrez, P. y Vega, M. (2016). Blockade of the Interaction of Calcineurin with FOXO in Astrocytes Protects Against Amyloid-βInduced Neuronal Death. Journal of Alzheimer's Disease, 52 (4)
dc.identifier.issn1875-8908es
dc.identifier.urihttps://hdl.handle.net/11441/87652
dc.description.abstractAstrocytes actively participate in neuro-inflammatory processes associated to Alzheimer’s disease (AD), and other brain pathologies. We recently showed that an astrocyte-specific intracellular signaling pathway involving an interaction of the phosphatase calcineurin with the transcription factor FOXO3 is a major driver in AD associated pathological inflammation, suggesting a potential new druggable target for this devastating disease. We have now developed decoy molecules to interfere with calcineurin/FOXO3 interactions, and tested them in astrocytes and neuronal co-cultures exposed to amyloid-β (Aβ) toxicity. We observed that interference of calcineurin/FOXO3 interactions exerts a protective action against A-induced neuronal death and favors the production of a set of growth factors that we hypothesize form part of a cytoprotective pathway to resolve inflammation. Furthermore, interference of the A-induced interaction of calcineurin with FOXO3 by decoy compounds significantly decreased amyloid-β protein precursor (AβPP) synthesis, reduced the AβPP amyloidogenic pathway, resulting in lower Alevels, and blocked the expression of pro-inflammatory cytokines TNFα and IL-6 in astrocytes. Collectively, these data indicate that interrupting pro-inflammatory calcineurin/FOXO3 interactions in astrocytes triggered by Aβ accumulation in brain may constitute an effective new therapeutic approach in AD. Future studies with intranasal delivery, or brain barrier permeable decoy compounds, are warranted.es
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherIOS Presses
dc.relation.ispartofJournal of Alzheimer's Disease, 52 (4)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAlzheimer’s diseasees
dc.subjectAstrocyteses
dc.subjectCalcineurines
dc.subjectDecoy compoundses
dc.subjectFOXOes
dc.titleBlockade of the Interaction of Calcineurin with FOXO in Astrocytes Protects Against Amyloid-βInduced Neuronal Deathes
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/acceptedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Bioquímica y Biología Moleculares
dc.contributor.groupUniversidad de Sevilla. CTS257: Envejecimiento y Neurodegeneraciónes
idus.format.extent20es
dc.journaltitleJournal of Alzheimer's Diseasees
dc.publication.volumen52es
dc.publication.issue4es

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