Mostrar el registro sencillo del ítem

dc.contributor.authorFernández-Valenzuela, Juan José
dc.contributor.authorSánchez-Varo, Raquel María 
dc.contributor.authorMuñoz-Castro, Clara
dc.contributor.authorDe Castro Carratalá, Vanessa
dc.contributor.authorSánchez-Mejías, Elisabeth 
dc.contributor.authorNavarro, Victoria
dc.contributor.authorJimenez, Sebastian
dc.contributor.authorNúñez-Díaz, Cristina
dc.contributor.authorGómez-Arboledas, Ángela
dc.contributor.authorMoreno-González, Inés
dc.contributor.authorVizuete, Marisa
dc.contributor.authorDávila-Cansino, José Carlos 
dc.contributor.authorVitorica, Javier
dc.contributor.authorGutiérrez-Pérez, Antonia 
dc.date.accessioned2024-01-23T09:57:19Z
dc.date.available2024-01-23T09:57:19Z
dc.date.created2024
dc.date.issued2020-09-08
dc.identifier.citationFernandez-Valenzuela JJ, Sanchez-Varo R, Muñoz-Castro C, De Castro V, Sanchez-Mejias E, Navarro V, Jimenez S, Nuñez-Diaz C, Gomez-Arboledas A, Moreno-Gonzalez I, Vizuete M, Davila JC, Vitorica J, Gutierrez A. Enhancing microtubule stabilization rescues cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer's disease model. Sci Rep. 2020 Sep 8;10(1):14776. PMID: 32901091; PMCID: PMC7479116.es_ES
dc.identifier.other32901091
dc.identifier.urihttps://hdl.handle.net/10630/29014
dc.description.abstractIn Alzheimer's disease (AD), and other tauopathies, microtubule destabilization compromises axonal and synaptic integrity contributing to neurodegeneration. These diseases are characterized by the intracellular accumulation of hyperphosphorylated tau leading to neurofibrillary pathology. AD brains also accumulate amyloid-beta (Aβ) deposits. However, the effect of microtubule stabilizing agents on Aβ pathology has not been assessed so far. Here we have evaluated the impact of the brain-penetrant microtubule-stabilizing agent Epothilone D (EpoD) in an amyloidogenic model of AD. Three-month-old APP/PS1 mice, before the pathology onset, were weekly injected with EpoD for 3 months. Treated mice showed significant decrease in the phospho-tau levels and, more interesting, in the intracellular and extracellular hippocampal Aβ accumulation, including the soluble oligomeric forms. Moreover, a significant cognitive improvement and amelioration of the synaptic and neuritic pathology was found. Remarkably, EpoD exerted a neuroprotective effect on SOM-interneurons, a highly AD-vulnerable GABAergic subpopulation. Therefore, our results suggested that EpoD improved microtubule dynamics and axonal transport in an AD-like context, reducing tau and Aβ levels and promoting neuronal and cognitive protection. These results underline the existence of a crosstalk between cytoskeleton pathology and the two major AD protein lesions. Therefore, microtubule stabilizers could be considered therapeutic agents to slow the progression of both tau and Aβ pathology.es_ES
dc.description.sponsorshipInstituto de Salud Carlos III (ISCiii) cofinanciado con fondos FEDER de la Unión Europea. Proyectos FIS PI15/00796 y PI18/01557 (AG), PI15/00957 y PI18/01556 (JV), CIBERNED (CB06/05/1116 (AG) and CB06/05/0094 )JV); proyecto de la Universidad de Malaga PPIT.UMA. B1.2017/26 (RSV). JJFV y CMC becas FPU (Ministerio de Ciencia, Innovación y Universidades). RSV contrato postdoctoral Universidad de Malaga. IMG contrato postdoctoral Ramon y Cajal Program.es_ES
dc.language.isoenges_ES
dc.publisherSpringer Naturees_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAlzheimer, Enfermedad de - Modelos animaleses_ES
dc.subject.otherAlzheimer's diseasees_ES
dc.subject.otherTaues_ES
dc.subject.otherTransgenic mouse modelses_ES
dc.subject.otherEpothilone-Des_ES
dc.subject.otherNeurodegenerationes_ES
dc.subject.otherAmyloides_ES
dc.titleEnhancing microtubule stabilization rescues cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer's disease model.es_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.centroFacultad de Cienciases_ES
dc.identifier.doi10.1038/s41598-020-71767-4
dc.rights.ccAtribución 4.0 Internacional
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones_ES


Ficheros en el ítem

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

Atribución 4.0 Internacional
Excepto si se señala otra cosa, la licencia del ítem se describe como Atribución 4.0 Internacional