BMS-708163 and Nilotinib restore synaptic dysfunction in human embryonic stem cell-derived Alzheimer's disease models.
Sci Rep
; 6: 33427, 2016 09 19.
Article
em En
| MEDLINE
| ID: mdl-27641902
ABSTRACT
Alzheimer's disease (AD) is the most common form of dementia. Cellular AD models derived from human pluripotent stem cells are promising tools in AD research. We recently developed human embryonic stem cell-derived AD models which overexpress mutant Presenilin1 genes, and which exhibit AD phenotypes, including synaptic dysfunction. In this study, we found that our AD models showed reduced levels of RAB3A and SV2B proteins in the pre-synapses, which is a possible cause of electrophysiological abnormalities. Through the screening of chemical compounds using our AD models, we have identified Aß peptide inhibitors which decrease the concentration of Aß in culture supernatant. Among these, BMS-708163 and Nilotinib were found to improve the expression levels of RAB3A and SV2B proteins and to recover the electrophysiological function in our AD models. These results suggest that the AD models we developed are promising materials for the discovery of AD drugs that target the expression of pre-synaptic proteins and synaptic function.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxidiazóis
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Pirimidinas
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Sulfonamidas
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Sinapses
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Doença de Alzheimer
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Células-Tronco Embrionárias Humanas
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Modelos Biológicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article