In Vivo Characterization of ARN14140, a Memantine/Galantamine-Based Multi-Target Compound for Alzheimer's Disease
| Autor: | Roberta Caporaso, Michela Rosini, Elena Simoni, Anna Minarini, Johann Meunier, Tangui Maurice, Emeline Keller, Andrea Cavalli, Angelo Reggiani |
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| Přispěvatelé: | Reggiani, Angelo M., Simoni, Elena, Caporaso, Roberta, Meunier, Johann, Keller, Emeline, Maurice, Tangui, Minarini, Anna, Rosini, Michela, Cavalli, Andrea, Mécanismes moléculaires dans les démences neurodégénératives (MMDN), 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) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Amyloid Drug Evaluation Preclinical Mice Transgenic Disease Biology Pharmacology Neuroprotection Article [SCCO]Cognitive science 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Alzheimer Disease Memantine medicine Galantamine Animals ComputingMilieux_MISCELLANEOUS Multidisciplinary Amyloid beta-Peptides [SCCO.NEUR]Cognitive science/Neuroscience Neurodegeneration memantine galantamine multi-target compound Alzheimer’s disease medicine.disease Acetylcholinesterase Peptide Fragments 3. Good health Biomarker (cell) Disease Models Animal 030104 developmental biology chemistry Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2016, 6 (1), ⟨10.1038/srep33172⟩ |
| ISSN: | 2045-2322 |
| Popis: | Alzheimer’s disease (AD) is a chronic pathological condition that leads to neurodegeneration, loss of intellectual abilities, including cognition and memory, and ultimately to death. It is widely recognized that AD is a multifactorial disease, where different pathological cascades (mainly amyloid and tau) contribute to neural death and to the clinical outcome related to the disease. The currently available drugs for AD were developed according to the one-target, one-drug paradigm. In recent times, multi-target strategies have begun to play an increasingly central role in the discovery of more efficacious candidates for complex neurological conditions, including AD. In this study, we report on the in vivo pharmacological characterization of ARN14140, a new chemical entity, which was obtained through a multi-target structure-activity relationship campaign, and which showed a balanced inhibiting profile against the acetylcholinesterase enzyme and the NMDA receptor. Based on the initial promising biochemical data, ARN14140 is here studied in mice treated with the amyloidogenic fragment 25–35 of the amyloid-β peptide, a consolidated non-transgenic AD model. Sub-chronically treating animals with ARN14140 leads to a prevention of the cognitive impairment and of biomarker levels connected to neurodegeneration, demonstrating its neuroprotective potential as new AD agent. |
| Databáze: | OpenAIRE |
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