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).
| Original language | English |
|---|---|
| Pages (from-to) | 240-253 |
| Number of pages | 14 |
| Journal | Cell Death and Differentiation |
| Volume | 14 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2007 |
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- Cell Biology
Cite this
Role of the JNK pathway in NMDA-mediated excitotoxicity of cortical neurons. / Centeno, C.; Repici, M.; Chatton, J. Y.; Riederer, B. M.; Bonny, C.; Nicod, P.; Price, M.; Clarke, P. G H; Papa, S.; Franzoso, G.; Borsello, T.
In: Cell Death and Differentiation, Vol. 14, No. 2, 02.2007, p. 240-253.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of the JNK pathway in NMDA-mediated excitotoxicity of cortical neurons
AU - Centeno, C.
AU - Repici, M.
AU - Chatton, J. Y.
AU - Riederer, B. M.
AU - Bonny, C.
AU - Nicod, P.
AU - Price, M.
AU - Clarke, P. G H
AU - Papa, S.
AU - Franzoso, G.
AU - Borsello, T.
PY - 2007/2
Y1 - 2007/2
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=33846202874&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846202874&partnerID=8YFLogxK
U2 - 10.1038/sj.cdd.4401988
DO - 10.1038/sj.cdd.4401988
M3 - Article
C2 - 16794604
AN - SCOPUS:33846202874
VL - 14
SP - 240
EP - 253
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
SN - 1350-9047
IS - 2
ER -