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dc.contributor.authorCuadrado-Tejedor, Mar
dc.contributor.authorGarcía-Barroso, Carolina
dc.contributor.authorSánzhez-Arias, Juan Antonio
dc.contributor.authorMederos, Sara
dc.contributor.authorRabal, Obdulia
dc.contributor.authorUgarte, Ana
dc.contributor.authorFranco, Rafael
dc.contributor.authorPascual-Lucas, Maria
dc.contributor.authorSegura, Victor
dc.contributor.authorPerea, Gertrudis
dc.contributor.authorOyarzabal, Julen
dc.contributor.authorGarcía-Osta, Ana
dc.date.accessioned2024-02-05T12:57:24Z
dc.date.available2024-02-05T12:57:24Z
dc.date.issued2015
dc.identifier.citationCuadrado-Tejedor, M., Garcia-Barroso, C., Sanzhez-Arias, J. et al. (2015). Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer’s disease. Clinical Epigenetics 7(108). https://doi.org/10.1186/s13148-015-0142-9es
dc.identifier.issn1868-7083
dc.identifier.urihttp://hdl.handle.net/20.500.12020/1178
dc.description.abstractBackground: Given the implication of histone acetylation in memory processes, histone deacetylase inhibitors (HDACIs) have been postulated as potential modulators of cognitive impairment in Alzheimer's disease (AD). However, dose-dependent side effects have been described in patients with the currently available broad-spectrum HDACIs, explaining why their therapeutic potential has not been realized for chronic diseases. Here, by simultaneously targeting two independent enzyme activities, histone deacetylase (HDAC) and phosphodiesterase-5 (PDE5), we propose a novel mode of inhibitory action that might increase the therapeutic specificity of HDACIs. Results: The combination of vorinostat, a pan-HDACI, and tadalafil, a PDE5 inhibitor, rescued the long-term potentiation impaired in slices from APP/PS1 mice. When administered in vivo, the combination of these drugs alleviated the cognitive deficits in AD mice, as well as the amyloid and tau pathology, and it reversed the reduced dendritic spine density on hippocampal neurons. Significantly, the combination of vorinostat and tadalafil was more effective than each drug alone, both against the symptoms and in terms of disease modification, and importantly, these effects persisted after a 4-week washout period. Conclusions: The results highlight the pharmacological potential of a combination of molecules that inhibit HDAC and PDE5 as a therapeutic approach for AD treatment.es
dc.language.isoenes
dc.publisherBMCes
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleConcomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer's diseasees
dc.typearticlees
dc.identifier.doihttps://doi.org/10.1186/s13148-015-0142-9
dc.journal.titleClinical Epigeneticses
dc.page.initial108es
dc.page.final119es
dc.rights.accessRightsopenAccesses
dc.subject.areaCiencias Biomédicases
dc.subject.keywordAlzheimer’s diseasees
dc.subject.keywordAmyloides
dc.subject.keywordGene transcriptiones
dc.subject.keywordHistone deacetylasees
dc.subject.keywordMemoryes
dc.subject.keywordPhosphodiesterasees
dc.subject.keywordTaues
dc.subject.unesco32 Ciencias Médicases
dc.volume.number7es


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