Combining two repurposed drugs as a promising approach for Alzheimer's disease therapy.
Sci Rep
; 5: 7608, 2015 Jan 08.
Article
em En
| MEDLINE
| ID: mdl-25566747
ABSTRACT
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 (Aß) 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 Aß25-35 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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Taurina
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Baclofeno
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Reposicionamento de Medicamentos
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Doença de Alzheimer
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
França