Role of the JNK pathway in NMDA-mediated excitotoxicity of cortical neurons.
Cell Death Differ
; 14(2): 240-53, 2007 Feb.
Article
en En
| MEDLINE
| ID: mdl-16794604
ABSTRACT
Excitotoxic insults induce c-Jun N-terminal kinase (JNK) activation, which leads to neuronal death and contributes to many neurological conditions such as cerebral ischemia and neurodegenerative disorders. The action of JNK can be inhibited by the D-retro-inverso form of JNK inhibitor peptide (D-JNKI1), which totally prevents death induced by N-methyl-D-aspartate (NMDA) in vitro and strongly protects against different in vivo paradigms of excitotoxicity. To obtain optimal neuroprotection, it is imperative to elucidate the prosurvival action of D-JNKI1 and the death pathways that it inhibits. In cortical neuronal cultures, we first investigate the pathways by which NMDA induces JNK activation and show a rapid and selective phosphorylation of mitogen-activated protein kinase kinase 7 (MKK7), whereas the only other known JNK activator, mitogen-activated protein kinase kinase 4 (MKK4), was unaffected. We then analyze the action of D-JNKI1 on four JNK targets containing a JNK-binding domain MAPK-activating death domain-containing protein/differentially expressed in normal and neoplastic cells (MADD/DENN), MKK7, MKK4 and JNK-interacting protein-1 (IB1/JIP-1).
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Base de datos:
MEDLINE
Asunto principal:
Corteza Cerebral
/
N-Metilaspartato
/
Proteínas Quinasas JNK Activadas por Mitógenos
/
Neuronas
/
Neurotoxinas
Límite:
Animals
Idioma:
En
Revista:
Cell Death Differ
Año:
2007
Tipo del documento:
Article
País de afiliación:
Suiza