microRNA-9 attenuates amyloidß-induced synaptotoxicity by targeting calcium/calmodulin-dependent protein kinase kinase 2.
Mol Med Rep
; 9(5): 1917-22, 2014 May.
Article
en En
| MEDLINE
| ID: mdl-24603903
The calcium/calmodulin-dependent protein kinase kinase 2, adenosine monophosphate-activated protein kinase (CAMKK2-AMPK) pathway mediated amyloid ß42 (Aß42)-induced synaptotoxicity and blockage of CAMKK2-protected neurons against the effect of Aß42. Numerous microRNAs (miRNAs) were downregulated in response to Aß42, including miR-9, a synapse-enriched miRNA that is decreased in Alzheimer's disease. In the present study the effect of miR-9 on Aß42triggered CAMKK2-AMPK activation and the synaptotoxic impairment was investigated. Aß42 oligomers were identified to be capable of inducing CAMKK2-AMPK pathway activation, which was attenuated by miR-9 overexpression. CAMKK2 was predicted to be a target of miR-9 using Pictar and Targetscan 6.2 Bioinformatics' algorithms. A luciferase activity assay and western blot analysis confirmed that miR-9 significantly inhibited CAMKK2 expression. Additionally, overexpression of miR-9 was sufficient to restore Aß42-induced dendritic spine loss and rescued Aß42-induced τ phosphorylation at Ser-262 mediated by the CAMKK2-AMPK pathway. The results of the present study demonstrated that miR-9 attenuated Aß-induced synaptotoxicity by targeting CAMKK2.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sinapsis
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Péptidos beta-Amiloides
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MicroARNs
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Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina
Límite:
Animals
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Humans
Idioma:
En
Revista:
Mol Med Rep
Año:
2014
Tipo del documento:
Article
Pais de publicación:
Grecia