Chapter 24 NF-KappaB Dimers in the Regulation of Neuronal Survival

Ilenia Sarnico, Annamaria Lanzillotta, Marina Benarese, Manuela Alghisi, Cristina Baiguera, Leontino Battistin, PierFranco Spano, Marina Pizzi

Research output: Contribution to journalArticle

Abstract

Nuclear factor-kappaB (NF-κB) is a dimeric transcription factor composed of five members, p50, RelA/p65, c-Rel, RelB, and p52 that can diversely combine to form the active transcriptional dimer. NF-κB controls the expression of genes that regulate a broad range of biological processes in the central nervous system such as synaptic plasticity, neurogenesis, and differentiation. Although NF-κB is essential for neuron survival and its activation may protect neurons against oxidative-stresses or ischemia-induced neurodegeneration, NF-κB activation can contribute to inflammatory reactions and apoptotic cell death after brain injury and stroke. It was proposed that the death or survival of neurons might depend on the cell type and the timing of NF-κB activation. We here discuss recent evidence suggesting that within the same neuronal cell, activation of diverse NF-κB dimers drives opposite effects on neuronal survival. Unbalanced activation of NF-κB p50/RelA dimer over c-Rel-containing complexes contributes to cell death secondary to the ischemic insult. While p50/RelA acts as transcriptional inducer of Bcl-2 family proapoptotic Bim and Noxa genes, c-Rel dimers specifically promote transcription of antiapototic Bcl-xL gene. Changes in the nuclear content of c-Rel dimers strongly affect the threshold of neuron vulnerability to ischemic insult and agents, likewise leptin, activating a NF-κB/c-Rel-dependent transcription elicit neuroprotection in animal models of brain ischemia.

Original languageEnglish
Pages (from-to)351-362
Number of pages12
JournalInternational Review of Neurobiology
Volume85
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Sarnico, I., Lanzillotta, A., Benarese, M., Alghisi, M., Baiguera, C., Battistin, L., Spano, P., & Pizzi, M. (2009). Chapter 24 NF-KappaB Dimers in the Regulation of Neuronal Survival. International Review of Neurobiology, 85, 351-362. https://doi.org/10.1016/S0074-7742(09)85024-1