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    •   RIUMA Principal
    • Investigación
    • Biología Celular, Genética y Fisiología - (BCGF)
    • BCGF - Contribuciones a congresos científicos
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    •   RIUMA Principal
    • Investigación
    • Biología Celular, Genética y Fisiología - (BCGF)
    • BCGF - Contribuciones a congresos científicos
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    Microtubule stabilization reduces amyloid pathology and improves synaptic/memory deficits in APP/PS1 mice

    • Autor
      Sánchez-Varo, Raquel MaríaAutoridad Universidad de Málaga; Fernández-Valenzuela, Juan José; Muñoz-Castro, Clara; De Castro Carratalá, Vanessa; Sánchez-Mejías, ElisabetAutoridad Universidad de Málaga; Navarro, V; Jimenez, Sebastian; Nuñez-Diaz, Cristina; Gomez-Arboledas, Angela; Moreno-Gonzalez, Ines; Moyano, F; Vizuete, María Luisa; Dávila-Cansino, José CarlosAutoridad Universidad de Málaga; Vitorica Ferrández, Javier; Gutiérrez-Pérez, AntoniaAutoridad Universidad de Málaga
    • Fecha
      2021
    • Editorial/Editor
      Alzheimer disease & Parkinson disease Conference 2021
    • Palabras clave
      Alzheimer, Enfermedad de - Congresos; Glucoproteínas - Congresos
    • Resumen
      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.
    • URI
      https://hdl.handle.net/10630/21253
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    Ficheros
    Sanchez-Varo et al ADPD2021.pdf (293.1Kb)
    Colecciones
    • BCGF - Contribuciones a congresos científicos

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    REPOSITORIO INSTITUCIONAL UNIVERSIDAD DE MÁLAGA
    REPOSITORIO INSTITUCIONAL UNIVERSIDAD DE MÁLAGA
     

     

    REPOSITORIO INSTITUCIONAL UNIVERSIDAD DE MÁLAGA
    REPOSITORIO INSTITUCIONAL UNIVERSIDAD DE MÁLAGA