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dc.contributor.authorFernandez, Ana M.
dc.contributor.authorHervas, Ruben
dc.contributor.authorDominguez Fraile, Manuel
dc.contributor.authorGarrido Victoria, Navarro
dc.contributor.authorGómez Gutiérrez, Patricia
dc.contributor.authorVega, Miguel
dc.contributor.authorVitorica, Javier
dc.contributor.authorPérez González, Juan Jesús
dc.contributor.authorTorres Aleman, Ignacio
dc.contributor.otherUniversitat Politècnica de Catalunya. Departament d'Enginyeria Química
dc.date.accessioned2018-07-06T06:51:18Z
dc.date.available2018-07-06T06:51:18Z
dc.date.issued2016-01-01
dc.identifier.citationFernandez, A., Hervas, R., Dominguez , M., Garrido, N., Gomez, P., Vega, M., Vitorica, J., Perez, J., Torres, I. Blockade of the Interaction of Calcineurin with FOXO in Astrocytes Protects Against Amyloid-beta-Induced Neuronal Death. "Journal of alzheimers disease", 1 Gener 2016, vol. 52, núm. 4, p. 1471-1478.
dc.identifier.issn1387-2877
dc.identifier.urihttp://hdl.handle.net/2117/119017
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-beta (A beta) toxicity. We observed that interference of calcineurin/FOXO3 interactions exerts a protective action against A beta-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 beta-induced interaction of calcineurin with FOXO3 by decoy compounds significantly decreased amyloid-beta protein precursor (A beta PP) synthesis, reduced the A beta PP amyloidogenic pathway, resulting in lower A beta levels, and blocked the expression of pro-inflammatory cytokines TNF alpha and IL-6 in astrocytes. Collectively, these data indicate that interrupting pro-inflammatory calcineurin/FOXO3 interactions in astrocytes triggered by A beta 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.
dc.format.extent8 p.
dc.language.isoeng
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Spain
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.subjectÀrees temàtiques de la UPC::Enginyeria química
dc.subject.lcshAlzheimer's disease
dc.subject.lcshAstrocytes
dc.subject.lcshNeurochemistry
dc.subject.otherAlzheimer's disease
dc.subject.otherastrocytes
dc.subject.othercalcineurin
dc.subject.otherdecoy compounds
dc.subject.otherFoxo
dc.subject.otherprecursos protein
dc.subject.othergrowth-factor
dc.subject.otheralpha
dc.titleBlockade of the Interaction of Calcineurin with FOXO in Astrocytes Protects Against Amyloid-beta-Induced Neuronal Death
dc.typeArticle
dc.subject.lemacAlzheimer, Malaltia d'
dc.subject.lemacNeurobiologia molecular
dc.subject.lemacNeuroquímica
dc.contributor.groupUniversitat Politècnica de Catalunya. GBMI - Grup de Biotecnologia Molecular i Industrial
dc.identifier.doi10.3233/JAD-160149
dc.description.peerreviewedPeer Reviewed
dc.relation.publisherversionhttp://content.iospress.com/articles/journal-of-alzheimers-disease/jad160149
dc.rights.accessOpen Access
drac.iddocument18721692
dc.description.versionPostprint (author's final draft)
upcommons.citation.authorFernandez, A.; Hervas, R.; Dominguez, M.; Garrido, N.; Gomez, P.; Vega, M.; Vitorica, J.; Perez, J.; Torres, I.
upcommons.citation.publishedtrue
upcommons.citation.publicationNameJournal of alzheimers disease
upcommons.citation.volume52
upcommons.citation.number4
upcommons.citation.startingPage1471
upcommons.citation.endingPage1478


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