Mostra el registre d'ítem simple
Blockade of the interaction of calcineurin with foxo in astrocytes protects against Aß-induced neuronal death
dc.contributor.author | Hervas, Rubén |
dc.contributor.author | Dominguez Fraile, Manuel |
dc.contributor.author | Garrido, Victoria |
dc.contributor.author | Gomez-Gutierrez, Patricia |
dc.contributor.author | Pérez González, Juan Jesús |
dc.contributor.author | Torres Aleman, Ignacio |
dc.contributor.other | Universitat Politècnica de Catalunya. Departament d'Enginyeria Química |
dc.date.accessioned | 2016-09-23T12:25:44Z |
dc.date.available | 2016-09-23T12:25:44Z |
dc.date.issued | 2016-06-23 |
dc.identifier.citation | Hervas, R., Dominguez, M., Garrido, V., Gomez-Gutierrez, P., Perez, J., Torres, I. Blockade of the interaction of calcineurin with foxo in astrocytes protects against Aß-induced neuronal death. "Journal of alzheimers disease", 23 Juny 2016, vol. 52, núm. 4, p. 1471-1478. |
dc.identifier.issn | 1387-2877 |
dc.identifier.uri | http://hdl.handle.net/2117/90167 |
dc.description.abstract | Astrocytes 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-ß (Aß) toxicity. We observed that interference of calcineurin/FOXO3 interactions exerts a protective action against Aß-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 Aß-induced interaction of calcineurin with FOXO3 by decoy compounds significantly decreased amyloid-ß protein precursor (AßPP) synthesis, reduced the AßPP amyloidogenic pathway, resulting in lower Aß levels, and blocked the expression of pro-inflammatory cytokines TNFa and IL-6 in astrocytes. Collectively, these data indicate that interrupting pro-inflammatory calcineurin/FOXO3 interactions in astrocytes triggered by Aß 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.extent | 8 p. |
dc.language.iso | eng |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ |
dc.subject | Àrees temàtiques de la UPC::Enginyeria química |
dc.subject.lcsh | Alzheimer's disease |
dc.subject.other | Alzheimer’s disease |
dc.subject.other | astrocytes |
dc.subject.other | calcineurin |
dc.subject.other | decoy compounds |
dc.subject.other | FOXO |
dc.title | Blockade of the interaction of calcineurin with foxo in astrocytes protects against Aß-induced neuronal death |
dc.type | Article |
dc.subject.lemac | Alzheimer, Malaltia d' |
dc.contributor.group | Universitat Politècnica de Catalunya. GBMI - Grup de Biotecnologia Molecular i Industrial |
dc.identifier.doi | 10.3233/JAD-160149 |
dc.description.peerreviewed | Peer Reviewed |
dc.relation.publisherversion | http://content.iospress.com/articles/journal-of-alzheimers-disease/jad160149 |
dc.rights.access | Open Access |
local.identifier.drac | 18789753 |
dc.description.version | Postprint (author's final draft) |
local.citation.author | Hervas, R.; Dominguez, M.; Garrido, V.; Gomez-Gutierrez, P.; Perez, J.; Torres, I. |
local.citation.publicationName | Journal of alzheimers disease |
local.citation.volume | 52 |
local.citation.number | 4 |
local.citation.startingPage | 1471 |
local.citation.endingPage | 1478 |
Fitxers d'aquest items
Aquest ítem apareix a les col·leccions següents
-
Articles de revista [190]
-
Articles de revista [2.226]