RT Journal Article
T1 Enhancing microtubule stabilization rescues cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer's disease model.
A1 Fernández-Valenzuela, Juan José
A1 Sánchez-Varo, Raquel María
A1 Muñoz-Castro, Clara
A1 De Castro Carratalá, Vanessa
A1 Sánchez-Mejías, Elisabeth
A1 Navarro, Victoria
A1 Jimenez, Sebastian
A1 Núñez-Díaz, Cristina
A1 Gómez-Arboledas, Ángela
A1 Moreno-González, Inés
A1 Vizuete, Marisa
A1 Dávila-Cansino, José Carlos
A1 Vitorica Ferrández, Javier
A1 Gutiérrez-Pérez, Antonia
K1 Alzheimer, Enfermedad de - Modelos animales
AB In 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.
PB Springer Nature
YR 2020
FD 2020-09-08
LK https://hdl.handle.net/10630/29014
UL https://hdl.handle.net/10630/29014
LA eng
NO Fernandez-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.
NO Instituto 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.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026