Combining two repurposed drugs as a promising approach for Alzheimer's disease therapy
| Autor: | Emmanuel Vial, Damien Toulorge, Nathalie Cholet, Yannick Pereira, Rémy Steinschneider, Esther Graudens, Tangui Maurice, Julie Foucquier, Rodolphe Hajj, Ilya Chumakov, Serguei Nabirotchkin, Aude Milet, Daniel Cohen, Catherine Scart-Grès, Aurélie Boucard, Noelle Callizot, Mickaël Guedj, Sory Traoré, Viviane Bertrand |
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| Přispěvatelé: | Pharnext SAS, Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuro/Sys, Neuronexperts, Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université Montpellier 2 - Sciences et Techniques (UM2)-École pratique des hautes études (EPHE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Dynamique cellulaire et moléculaire de la muqueuse respiratoire, Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-École pratique des hautes études (EPHE), Maurice, Tangui, École pratique des hautes études (EPHE) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Baclofen Taurine Acamprosate Apoptosis Mice Transgenic Neuroprotection Article Transgenic Model Amyloid beta-Protein Precursor Mice Glutamatergic [SCCO]Cognitive science Alzheimer Disease In vivo Animals Humans Medicine Rats Wistar Cells Cultured ComputingMilieux_MISCELLANEOUS Neurons Amyloid beta-Peptides Multidisciplinary business.industry [SCCO.NEUR]Cognitive science/Neuroscience [SCCO.NEUR] Cognitive science/Neuroscience Drug Repositioning Glutamate receptor Drug Synergism [SCCO] Cognitive science medicine.disease Peptide Fragments Rats 3. Good health Disease Models Animal Drug repositioning Neuroprotective Agents Female Alzheimer's disease business Neuroscience Signal Transduction medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2015, 5 (1), ⟨10.1038/srep07608⟩ Scientific Reports, 2015, 5 (1), ⟨10.1038/srep07608⟩ |
| ISSN: | 2045-2322 |
| Popis: | Alzheimer disease (AD) represents a major medical problem where mono-therapeutic interventions demonstrated only a limited efficacy so far. We explored the possibility of developing a combinational therapy that might prevent the degradation of neuronal and endothelial structures in this disease. We argued that the distorted balance between excitatory (glutamate) and inhibitory (GABA/glycine) systems constitutes a therapeutic target for such intervention. We found that a combination of two approved drugs – acamprosate and baclofen – synergistically protected neurons and endothelial structures in vitro against amyloid-beta (Aβ) oligomers. The neuroprotective effects of these drugs were mediated by modulation of targets in GABA/glycinergic and glutamatergic pathways. In vivo, the combination alleviated cognitive deficits in the acute Aβ25–35 peptide injection model and in the mouse mutant APP transgenic model. Several patterns altered in AD were also synergistically normalised. Our results open up the possibility for a promising therapeutic approach for AD by combining repurposed drugs. |
| Databáze: | OpenAIRE |
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