Post-ischemic brain damage: NF-kappaB dimer heterogeneity as a molecular determinant of neuron vulnerability.
Nuclear factor-kappaB (NF-kappaB) has been proposed to serve a dual function as a regulator of neuron survival in pathological conditions associated with neurodegeneration. NF-kappaB is a transcription family of factors comprising five different proteins, namely p50, RelA/p65, c-Rel, RelB and p52, which can combine differently to form active dimers in response to external stimuli. Recent research shows that diverse NF-kappaB dimers lead to cell death or cell survival in neurons exposed to ischemic injury. While the p50/p65 dimer participates in the pathogenesis of post-ischemic injury by inducing pro-apoptotic gene expression, c-Rel-containing dimers increase neuron resistance to ischemia by inducing anti-apoptotic gene transcription. We present, in this report, the latest findings and consider the therapeutic potential of targeting different NF-kappaB dimers to limit ischemia-associated neurodegeneration.
Pizzi
Marina
M
Division of Pharmacology and Experimental Therapeutics, Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia, Italy. pizzi@med.unibs.it
Sarnico
Ilenia
I
Lanzillotta
Annamaria
A
Battistin
Leontino
L
Spano
PierFranco
P
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001925:Brain Damage, Chronic / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D019281:Dimerization; D005786:Gene Expression Regulation; D006801:Humans; D016328:NF-kappa B / Q000502:physiology*; D009474:Neurons / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism
D016328:NF-kappa B; D014157:Transcription Factors