Mutant presenilin-1 induces apoptosis and downregulates Akt/PKB.
J Neurosci
; 19(13): 5360-9, 1999 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-10377346
Most early onset cases of familial Alzheimer's disease (AD) are caused by mutations in presenilin-1 (PS1) and presenilin-2 (PS2). These mutations lead to increased beta-amyloid formation and may induce apoptosis in some model systems. Using primary cultured hippocampal neurons (HNs) and rat pheochromocytoma (PC12) cells transiently transfected with replication-defective recombinant adenoviral vectors expressing wild-type or mutant PS1, we demonstrate that mutant PS1s induce apoptosis, downregulate the survival factor Akt/PKB, and affect several Akt/PKB downstream targets, including glycogen synthase kinase-3beta and beta-catenin. Expression of a constitutively active Akt/PKB rescues HNs from mutant PS1-induced neuronal cell death, suggesting a potential therapeutic target for AD. Downregulation of Akt/PKB may be a mechanism by which mutant PS1 induces apoptosis and may play a role in the pathogenesis of familial AD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación hacia Abajo
/
Transactivadores
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Proteínas Serina-Treonina Quinasas
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Apoptosis
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Proteínas Quinasas Activadas por Mitógenos
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Receptor trkA
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Proteínas de Pez Cebra
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Proteínas de la Membrana
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Mutación
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Neuronas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Neurosci
Año:
1999
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos