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dc.contributor.authorSanchez-Varo, Raquel
dc.contributor.authorFernandez-Valenzuela, Juan José
dc.contributor.authorDe Castro, Vanessa
dc.contributor.authorSanchez-Mejias, Elisabeth
dc.contributor.authorNuñez-Diaz, Cristina
dc.contributor.authorGómez-Arboledas, Ángela
dc.contributor.authorMoreno González, Inés
dc.contributor.authorDavila, Jose Carlos 
dc.contributor.authorVitorica, Javier
dc.contributor.authorGutierrez-Perez, Antonia 
dc.date.accessioned2020-12-17T16:42:19Z
dc.date.available2020-12-17T16:42:19Z
dc.date.created2020-12
dc.date.issued2020-12-17
dc.identifier.urihttps://hdl.handle.net/10630/20629
dc.description.abstractCognitive decline in Alzheimer's disease (AD) is highly related to synaptic dysfunction and neuronal loss. In AD, the hyperphosphorylation of tau compromises axonal transport and leads to the generation of dystrophic neurites, contributing to synaptic impairment. In addition to phospho-tau, AD brains accumulate amyloid-beta. This study evaluated the effect of the brain-penetrant microtubule-stabilizing agent, Epothilone D (EpoD) in the progression of the disease in a double transgenic mouse model of amyloidosis. Young APP/PS1 mice were weekly treated with intraperitoneal injections of EpoD (2 mg/kg) or vehicle solution for 3 months. Memory performance was tested using object-recognition tasks, Y-maze and Morris water maze. EpoD-treated mice improved their performance of cognitive tests, while hippocampal phospho-tau and Aβ levels, especially soluble oligomers, decreased significantly. β/γ-secretase activities were not affected by EpoD in vitro. A significant amelioration of synaptic/neuritic pathology was found. Remarkably, EpoD exerted a neuroprotective effect on SOM-interneurons, a highly AD-vulnerable GABAergic subpopulation. In conclusion, EpoD improved microtubule dynamics and axonal transport in an AD-like context, reducing tau and Abeta accumulation, and promoting neuronal and cognitive protection. These results underline the crosstalk between cytoskeleton pathology and proteinopathy. Therefore, microtubule-stabilizing drugs could be candidates for slowing AD progression at both tau and Aβ pathologies.es_ES
dc.description.sponsorshipSupported by PI18/01557 (to AG) and PI18/01556 (to JV) grants from ISCiii of Spain, co-financed by FEDER funds from European Union, CIBERNED collaborative grant (to AG and JV), and by PPIT.UMA.B1.2017/26 grant (to RSV). Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.es_ES
dc.language.isoenges_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectAlzheimer, enfermedad dees_ES
dc.subjectSistema nervioso - Degeneraciónes_ES
dc.subject.otherAlzheimeres_ES
dc.subject.otherEpothilone Des_ES
dc.subject.othertransgenic modeles_ES
dc.subject.otherneurodegenerationes_ES
dc.titleMicrotubule stabilization protects cognitive function and slows down the course of Alzheimer's like pathology in an amyloidogenic mouse modeles_ES
dc.typeinfo:eu-repo/semantics/conferenceObjectes_ES
dc.centroFacultad de Cienciases_ES
dc.relation.eventtitleNeurodegenerative Diseases: Biology and Therapeuticses_ES
dc.relation.eventplaceVirtual meetinges_ES
dc.relation.eventdate12/2020es_ES


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