FDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on cbp and protect against proteotoxicity.
PLoS One
; 6(11): e27762, 2011.
Article
em En
| MEDLINE
| ID: mdl-22114686
ABSTRACT
Screening a library of drugs with known safety profiles in humans yielded 30 drugs that reliably protected mammalian neurons against glucose toxicity. Subsequent screening demonstrated that 6 of these 30 drugs increase lifespan in C. elegans caffeine, ciclopirox olamine, tannic acid, acetaminophen, bacitracin, and baicalein. Every drug significantly reduced the age-dependent acceleration of mortality rate. These protective effects were blocked by RNAi inhibition of cbp-1 in adults only, which also blocks protective effects of dietary restriction. Only 2 drugs, caffeine and tannic acid, exhibited a similar dependency on DAF-16. Caffeine, tannic acid, and bacitracin also reduced pathology in a transgenic model of proteotoxicity associated with Alzheimer's disease. These results further support a key role for glucose toxicity in driving age-related pathologies and for CBP-1 in protection against age-related pathologies. These results also provide novel lead compounds with known safety profiles in human for treatment of age-related diseases, including Alzheimer's disease and diabetic complications.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Envelhecimento
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Preparações Farmacêuticas
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Aprovação de Drogas
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Proteínas de Caenorhabditis elegans
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Histona Acetiltransferases
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Doença de Alzheimer
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Glucose
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Neurônios
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article