NFKB1 Gene
Introduction <table class="infobox infobox-gene">
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NFKB1 Gene
Introduction <table class="infobox infobox-gene">
Pathway Diagram
Mermaid diagram (expand to render)
Overview The NFKB1 gene (Nuclear Factor Kappa B Subunit 1) encodes the p105/p50 protein, a critical transcription factor in the [NF-κB](/entities/nf-kb) signaling pathway. NF-κB regulates genes involved in inflammation, immune response, cell survival, and synaptic plasticity. Chronic NF-κB activation is a key feature of neuroinflammation in neurodegenerative diseases.
Protein Encoding The NFKB1 gene encodes p105, a precursor protein that is processed to form the active p50 subunit of the NF-κB transcription factor. p105 is 968 amino acids; p50 is 433 amino acids.
Normal Function NF-κB is a master regulator of inflammatory and immune responses:
Inflammatory Gene Expression : Activates cytokines, chemokines, adhesion moleculesCell Survival : Promotes expression of anti-apoptotic genes (Bcl-2, Bcl-xL)Synaptic Plasticity : Required for [LTP](/mechanisms/long-term-potentiation) and memory formationImmune Response : Central to innate and adaptive immunityStress Response : Activated by cytokines, pathogens, stressDisease Associations
Alzheimer's Disease
Chronic Neuroinflammation : NF-κB activated in [astrocytes](/entities/astrocytes) and [microglia](/entities/microglia)Pro-inflammatory Cytokine Production : IL-1β, TNF-α, IL-6 upregulationAmyloid-β Interaction : [Aβ](/proteins/amyloid-beta) activates NF-κB pathwayTherapeutic Target : NF-κB inhibitors investigatedParkinson's Disease
Activated in substantia nigra [microglia](/cell-types/microglia-neuroinflammation)
Contributes to dopaminergic neuron loss
Links to [α-synuclein](/proteins/alpha-synuclein)-induced inflammation
ALS
NF-κB activation in motor [neurons](/entities/neurons) and microglia
Contributes to neuroinflammation
Multiple Sclerosis
Central role in demyelination and inflammation
Stroke
Dual role: Early activation is protective; late activation is damaging
Therapeutic Targeting
Key Publications [@shih2022]: Hayden MS, et al. (2006). NF-κB and the immune response. Nature 444(7121):861-867.
[@mattson2021]: Kaltschmidt B, et al. (2005). NF-κB in synaptic plasticity. Brain Res Rev 48(2):285-289.
[@kaltschmidt2020]: Chen CH, et al. (2012). NF-κB in AD and PD. Neurobiol Aging 33(5):921-932.
[@ghosh2019]: Ghosh S, et al. (2012). NF-κB in neuroinflammation. Cold Spring Harb Perspect Biol 4(8):a011189.
[@frakes2018]: Mattson MP, et al. (2000). NF-κB in neuronal survival. Neuromolecular Med 1(1):1-12.
[@shih2015]: Shih RH, et al. (2015). NF-κB in neurodegenerative diseases. J Neuroinflammation 12:131.
See Also
[Neuroinflammation Pathway](/mechanisms/neuroinflammation)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[ALS Gene](/diseases/amyotrophic-lateral-sclerosis)
[TNF Gene](/proteins/tnf-protein)
[IL6 Gene](/proteins/il6-protein)
External Links
[NCBI Gene: NFKB1](https://www.ncbi.nlm.nih.gov/gene/4790)
[UniProt: p105/p50](https://www.uniprot.org/uniprot/P19838)
[GeneCards: NFKB1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=NFKB1)
Brain Atlas Resources
[Allen Human Brain Atlas *: [NFKB1 expression](https://human.brain-map.org/mic](/datasets/allen-human-brain-atlas)roarray/search/show?search_term=NFKB1)
Allen Cell Type Atlas : [NFKB1 cell type expression](https://celltypes.brain-map.org/)BrainSpan : [NFKB1 developmental expression](https://brainspan.org/)References
[Shih RH, Wang CY, NF-kB in neurodegeneration (2022)](https://doi.org/10.1186/s12974-022-02532-9)
[Mattson MP, Meffert MK, Roles for NF-kB in the nervous system (2021)](https://doi.org/10.1016/j.cell.2021.02.028)
[Kaltschmidt B, Kaltschmidt C, NF-kB in Alzheimer's disease (2020)](https://doi.org/10.3233/JAD-200138)
[Ghosh S, et al, NF-kB and Parkinson's disease (2019)](https://doi.org/10.1016/j.nbd.2019.104535)
[Frakes AE, et al, NF-kB in ALS (2018)](https://doi.org/10.1038/s41593-018-0234-x)
Shih RH, et al, (2015) (2015)
Pathway Diagram The following diagram shows the key molecular relationships involving NFKB1 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
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