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Microtubule stabilization reduces amyloid pathology and improves synaptic/memory deficits in APP/PS1 mice
dc.contributor.author | Sánchez-Varo, Raquel María | |
dc.contributor.author | Fernández-Valenzuela, Juan José | |
dc.contributor.author | Muñoz-Castro, Clara | |
dc.contributor.author | De Castro Carratalá, Vanessa | |
dc.contributor.author | Sánchez-Mejías, Elisabeth | |
dc.contributor.author | Navarro, Victoria | |
dc.contributor.author | Jiménez, Sebastián | |
dc.contributor.author | Núñez-Díaz, Cristina | |
dc.contributor.author | Gómez-Arboledas, Ángela | |
dc.contributor.author | Moreno-Gonzalez, Ines | |
dc.contributor.author | Moyano, F | |
dc.contributor.author | Vizuete, María Luisa | |
dc.contributor.author | Dávila-Cansino, José Carlos | |
dc.contributor.author | Vitorica Ferrández, Javier | |
dc.contributor.author | Gutiérrez-Pérez, Antonia | |
dc.date.accessioned | 2021-03-23T10:49:27Z | |
dc.date.available | 2021-03-23T10:49:27Z | |
dc.date.created | 2021-03-23 | |
dc.date.issued | 2021 | |
dc.identifier.uri | https://hdl.handle.net/10630/21253 | |
dc.description.abstract | Aims: Cognitive decline in Alzheimer's disease (AD) is highly related to synaptic/neuronal loss. Tau hyperphosphorylation destabilizes microtubules leading to axonal transport failure and generation of dystrophic neurites, thus contributing to synaptic dysfunction. The effect of microtubule stabilization on amyloid-beta pathology has not been assessed in vivo yet. This study evaluated the effect of the microtubule-stabilizing agent, Epothilone D (EpoD) in the pathology of an amyloidogenic mouse model. Methods: APP751SL/PS1M146L mice (3-month-old) were treated weekly with intraperitoneal injections of EpoD (2 mg/kg) or vehicle for 3 months. For memory performance, animals were tested on the objectrecognition, Y-maze and Morris water maze. Hippocampal proteinopathies were quantified by image analysis after immunostaining. Somatostatin (SOM)-numerical density was calculated by stereology. APPswe-N2a cells were treated with EpoD 100nM for 12/24 hours. Protein levels were analysed by Western/dot-blot. Results: EpoD-treated mice improved their performance of cognitive tests, while hippocampal phospho-tau and Ab (especially oligomers) accumulation decreased, together with synaptic/neuritic pathology. Remarkably, EpoD exerted a neuroprotective effect on SOM-interneurons, a highly AD-vulnerable GABAergic subpopulation. Conclusions: EpoD improved microtubule dynamics and axonal transport in an AD-like context, reducing tau and Ab accumulation and promoting neuronal and cognitive protection, underlining the cross-talk between cytoskeleton pathology and proteinopathy. Therefore, microtubule-stabilizing drugs could be candidates for slowing AD at both tau and Ab pathologies. | es_ES |
dc.description.sponsorship | Supported by PI18/01557 (to AG) and PI18/01556 (to JV) grants from ISCiii of Spain, co-financed by FEDER funds (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.iso | eng | es_ES |
dc.publisher | Alzheimer disease & Parkinson disease Conference 2021 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | Alzheimer, Enfermedad de - Congresos | es_ES |
dc.subject | Glucoproteínas - Congresos | es_ES |
dc.subject.other | Therapeutic target | es_ES |
dc.subject.other | Alzheimer disease | es_ES |
dc.subject.other | Microtubule | es_ES |
dc.subject.other | Amyloid beta | es_ES |
dc.title | Microtubule stabilization reduces amyloid pathology and improves synaptic/memory deficits in APP/PS1 mice | es_ES |
dc.type | info:eu-repo/semantics/conferenceObject | es_ES |
dc.centro | Facultad de Ciencias | es_ES |
dc.relation.eventtitle | AD/PD™ 2021, Alzheimer's & Parkinson's Diseases Conference | es_ES |
dc.relation.eventplace | Virtual | es_ES |
dc.relation.eventdate | 09/03/2021 - 14/03/2021 | es_ES |