Enhancing microtubule stabilization rescues cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer's disease model

التفاصيل البيبلوغرافية
العنوان:	Enhancing microtubule stabilization rescues cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer's disease model
المؤلفون:	Fernandez-Valenzuela, Juan Jose, Sanchez-Varo, Raquel, Muñoz-Castro, Clara, De Castro, Vanessa, Sanchez-Mejias, Elisabeth, Navarro, Victoria, Jimenez, Sebastian, Nuñez-Diaz, Cristina, Gomez-Arboledas, Angela, Moreno-Gonzalez, Ines, Vizuete, Marisa, Davila, Jose Carlos, Vitorica, Javier, Gutierrez, Antonia
المساهمون:	Fernandez-Valenzuela,JJ, Sanchez-Varo,R, De Castro,V, Sanchez-Mejias,E, Nuñez-Diaz,C, Gomez-Arboledas,A, Moreno-Gonzalez,I, Davila,JC, Gutierrez,A Dpto. Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga‑IBIMA, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain. Fernandez-Valenzuela,JJ, Muñoz-Castro,C, Navarro,V, Jimenez,S, Vizuete,M, Vitorica,J, Gutierrez,A Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. Muñoz-Castro,C, Vitorica,J Dpto. Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain. Muñoz-Castro,C, Vitorica,J Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio/CSIC, Universidad de Sevilla, Sevilla, Spain., This study was supported by Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grants PI15/00796 and PI18/01557 (both to AG), PI15/00957 and PI18/01556 (both to JV), and CIBERNED (CB06/05/1116 to AG and CB06/05/0094 to JV), by Malaga University grant PPIT.UMA.B1.2017/26 (to RSV). JJFV and CMC were supported by FPU PhD fellowships (Spanish Ministry of Science, Innovation and Universities). RSV held a postdoctoral contract from Malaga University. IMG is recipient of a senior postdoctoral contract from Ramon y Cajal Program (Spain Government).
بيانات النشر:	Springer Nature
سنة النشر:	2020
المجموعة:	Sistema Sanitario Público de Andalucía (SSPA): Repositorio
مصطلحات موضوعية:	Amyloid, Alzheimer disease, Axonal transport, Brain, Interneurons, Tauopathies, Amiloide, Enfermedad de Alzheimer, Transporte axonal, Encéfalo, Interneuronas, Tauopatías, Medical Subject Headings::Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease, Medical Subject Headings::Organisms::Eukaryota::Animals, Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cytoplasmic Streaming::Axonal Transport, Medical Subject Headings::Psychiatry and Psychology::Mental Disorders::Delirium, Dementia, Amnestic, Cognitive Disorders::Cognition Disorders, Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Lactones::Macrolides::Epothilones, Medical Subject Headings::Check Tags::Female, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans, Medical Subject Headings::Check Tags::Male, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice, Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic, Medical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Cytoskeleton::Microtubules, Medical Subject Headings::Anatomy::Nervous System::Neurons, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype
الوصف:	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. ; Yes
نوع الوثيقة:	article in journal/newspaper
وصف الملف:	application/pdf
اللغة:	English
تدمد:	2045-2322
Relation:	https://www.nature.com/articles/s41598-020-71767-4; Fernandez-Valenzuela JJ, Sanchez-Varo R, Muñoz-Castro C, De Castro V, Sanchez-Mejias E, Navarro V, et al. 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; http://hdl.handle.net/10668/3590; PMC747911
DOI:	10.1038/s41598-020-71767-4
الاتاحة:	http://hdl.handle.net/10668/3590 https://doi.org/10.1038/s41598-020-71767-4
Rights:	Atribución 4.0 Internacional ; http://creativecommons.org/licenses/by/4.0/ ; open access
رقم الانضمام:	edsbas.11C3668B
قاعدة البيانات:	BASE

View record in BASE

Full Text Finder

الوصف
تدمد:	20452322
DOI:	10.1038/s41598-020-71767-4