c-Jun N-terminal kinase regulates soluble Aß oligomers and cognitive impairment in AD mouse model.
J Biol Chem
; 286(51): 43871-43880, 2011 Dec 23.
Article
en En
| MEDLINE
| ID: mdl-22033930
ABSTRACT
Alzheimer disease (AD) is characterized by cognitive impairment that starts with memory loss to end in dementia. Loss of synapses and synaptic dysfunction are closely associated with cognitive impairment in AD patients. Biochemical and pathological evidence suggests that soluble Aß oligomers correlate with cognitive impairment. Here, we used the TgCRND8 AD mouse model to investigate the role of JNK in long term memory deficits. TgCRND8 mice were chronically treated with the cell-penetrating c-Jun N-terminal kinase inhibitor peptide (D-JNKI1). D-JNKI1, preventing JNK action, completely rescued memory impairments (behavioral studies) as well as the long term potentiation deficits of TgCRND8 mice. Moreover, D-JNKI1 inhibited APP phosphorylation in Thr-668 and reduced the amyloidogenic cleavage of APP and Aß oligomers in brain parenchyma of treated mice. In conclusion, by regulating key pathogenic mechanisms of AD, JNK might hold promise as innovative therapeutic target.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Regulación Enzimológica de la Expresión Génica
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Péptidos beta-Amiloides
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Proteínas Quinasas JNK Activadas por Mitógenos
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Enfermedad de Alzheimer
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2011
Tipo del documento:
Article
País de afiliación:
Italia