NF-kappaB signaling in cerebral ischemia.
Neuroscience
; 158(3): 995-1006, 2009 Feb 06.
Article
em En
| MEDLINE
| ID: mdl-18675321
ABSTRACT
The transcription factor NF-kappaB is a key regulator of hundreds of genes involved in cell survival and inflammation. There is ample evidence that NF-kappaB is activated in cerebral ischemia, mainly in neurons. Despite its well known role as an antiapoptotic factor, in cerebral ischemia NF-kappaB contributes to neuronal cell death, at least if the ischemia is severe enough to lead to irreversible brain damage. In contrast, NF-kappaB also seems to be responsible for the preconditioning effect of a transient and sublethal ischemia, perhaps by dampening its own subsequent full activation. Among the five NF-kappaB subunits, RelA and p50 are responsible for the detrimental effect in cerebral ischemia. Activation of NF-kappaB signaling is mediated by the upstream kinase inhibitor of kappaB kinase and is triggered by hypoxia, reactive oxygen species, and several inflammatory mediators. Interestingly, the complex NF-kappaB signaling pathway provides drug targets at several levels. Modulation of NF-kappaB signaling has the potential to interrupt multiple inflammatory and apoptotic mechanisms through one specific molecular target.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Isquemia Encefálica
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NF-kappa B
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Apoptose
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Encefalite
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Degeneração Neural
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article