Post-ischemic brain damage: NF-κB dimer heterogeneity as a molecular determinant of neuron vulnerability

Abstract

Nuclear factor-kappaB (NF-κB) has been proposed to serve a dual function as a regulator of neuron survival in pathological conditions associated with neurodegeneration. NF-κB 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-κB 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-κB dimers to limit ischemia-associated neurodegeneration.