Important neuronal toxicity of microtubule-bound Tau in vivo in Drosophila
| Autor: | Yoan Arribat, Magalie Lecourtois, Christelle Redt-Clouet, Sébastien Feuillette, Marie-Laure Parmentier, Anne-Laure Bougé, Yasmina Talmat-Amar |
|---|---|
| Přispěvatelé: | Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2011 |
| Předmět: |
Male
Tau protein tau Proteins Neuronal toxicity Axonal Transport Microtubules Animals Genetically Modified 03 medical and health sciences 0302 clinical medicine Microtubule In vivo mental disorders Genetics medicine Animals Humans Protein Isoforms Phosphorylation Axon Molecular Biology ComputingMilieux_MISCELLANEOUS Genetics (clinical) 030304 developmental biology Neurons 0303 health sciences biology General Medicine Anatomy Cell biology Disease Models Animal medicine.anatomical_structure Tauopathies Toxicity biology.protein Axoplasmic transport [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Drosophila Female 030217 neurology & neurosurgery Function (biology) |
| Zdroj: | Human Molecular Genetics Human Molecular Genetics, Oxford University Press (OUP), 2011, 20 (19), pp.3738-3745. ⟨10.1093/hmg/ddr290⟩ |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | The microtubule-associated protein Tau is found in large amount in axons of neurons and is involved in human neurodegenerative diseases called tauopathies, which include Alzheimer's disease. In these diseases, the Tau protein is abnormally hyperphosphorylated and one therapeutic strategy currently under consideration consists in inhibiting Tau phosphorylation. However, the consequences of an excess of hypophosphorylated Tau onto neuronal physiology have not been investigated in vivo. Here we studied how important is Tau phosphorylation for axonal transport and neurohormone release in vivo, using the Drosophila model. Surprisingly, our results demonstrate a stronger toxicity of hypophosphorylated Tau for neuronal function, when compared with normal or pseudophosphorylated Tau. This reveals a potential limit of the current therapeutic strategy aimed at inhibiting Tau phosphorylation. |
| Databáze: | OpenAIRE |
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