Okadaic acid increases autophagosomes in rat neurons: implications for Alzheimer's disease.
J Neurosci Res
; 86(14): 3230-9, 2008 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-18615642
ABSTRACT
Autophagosomes are accumulated in Alzheimer's disease (AD), but the regulatory pathway of autophagy in AD remains largely unknown. By using electron microscopy, Western blotting, and immunocytochemistry, here we show that autophagosomes are accumulated in rat neurons by okadaic acid (OA), a protein phosphatase-2A inhibitor known to enhance tau phosphorylation, beta-amyloid (Abeta) deposition, and neuronal death, which are the pathological hallmarks of AD. Autophagy can be generally induced via several distinct pathways, such as inhibition of mTOR or activation of beclin-1. Interestingly, OA increased both mTOR and beclin-1 pathways simultaneously, which suggests that autophagy in OA-treated neurons is induced mainly via the beclin-1 pathway, and less so via mTOR inhibition. Finally, inhibition of autophagy by 3MA reduced cytotoxicity in OA-treated neurons. Our novel findings provide new insights into the pathology of and therapeutic intervention for AD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fagossomos
/
Ácido Okadáico
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Inibidores Enzimáticos
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Doença de Alzheimer
/
Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article