期刊
FRONTIERS IN MOLECULAR NEUROSCIENCE
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2015.00069
关键词
NF-kappaB; long-term memory; transcription factors; synapse; dentate gyrus; long term potentiation
资金
- German Research Council (DFG)
- Walcker Stiftung, Isny, Germany
- University of Bielefeld
The transcription factor nuclear factor kappaB (NF-kappa B) is a well-known regulator of inflammation, stress, and immune responses as well as cell survival. In the nervous system, NF-kappa B 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-kappa B 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-kappa B regulates neuroprotection, neuronal transmission, and long-term memory. In addition, after genetic ablation of all NF-kappa B 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-kappa B target gene PKAcat and other downstream target genes such as Igf2 are critically involved. Therefore, NF-kappa B 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-kappa B in neurons, we will discuss on a neuroinflammatory role of the transcription factor in glia. Finally, a model for NF-kappa B homeostasis on the molecular level is presented, in order to explain seemingly the contradictory, the friend or foe, role of NF-kappa B in the nervous system.
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