Abstract
The transcription factor nuclear factor kappaB (NF-κB) is a well-known regulator of inflammation, stress, and immune responses as well as cell survival. In the nervous system, NF-κB is one of the crucial components in the molecular switch that converts short- to long-term memory—a process that requires de novo gene expression. Here, the researches published on NF-κB and downstream target genes in mammals will be reviewed, which are necessary for structural plasticity and long-term memory, both under normal and pathological conditions in the brain. Genetic evidence has revealed that NF-κB regulates neuroprotection, neuronal transmission, and long-term memory. In addition, after genetic ablation of all NF-κB subunits, a severe defect in hippocampal adult neurogenesis was observed during aging. Proliferation of neural precursors is increased; however, axon outgrowth, synaptogenesis, and tissue homeostasis of the dentate gyrus are hampered. In this process, the NF-κB target gene PKAcat and other downstream target genes such as Igf2 are critically involved. Therefore, NF-κB activity seems to be crucial in regulating structural plasticity and replenishment of granule cells within the hippocampus throughout the life. In addition to the function of NF-κB in neurons, we will discuss on a neuroinflammatory role of the transcription factor in glia. Finally, a model for NF-κB homeostasis on the molecular level is presented, in order to explain seemingly the contradictory, the friend or foe, role of NF-κB in the nervous system.
Highlights
TO NF-κBNF-κB is a master transcription factor that is ubiquitously expressed and responds to diverse stimuli including cytokines, growth factors, and bacteria or viruses by the expression of stress response genes in many cells (Hayden and Ghosh, 2012)
We found that pre-conditioning neurons with tumor necrosis factor alpha (TNF) or low amounts of amyloid beta peptide (Aβ) could protect neurons against Aβ-mediated neurotoxicity (Kaltschmidt et al, 1999)
Previous reviews suggested that the two secreted proteins, brain-derived neurotrophic factor (BDNF) and tissue plasminogen activator, have been repeatedly implicated in lasting long-term potentiation (L-LTP) as memory-relevant cAMP response element-binding protein (CREB) target genes (Kandel, 2001) or nNOS and presenilin as additional CREB targets (West et al, 2002)
Summary
TO NF-κBNF-κB is a master transcription factor that is ubiquitously expressed and responds to diverse stimuli including cytokines, growth factors, and bacteria or viruses by the expression of stress response genes in many cells (Hayden and Ghosh, 2012). This work underscores the importance of transcription factors such as c-FOS for the formation of long-term memory in specific neurons (engram cells).
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