Nuclear factor kappa B (NF-κB) is a family of transcription factors that regulate genes involved in inflammation, cell survival, immune responses, and synaptic plasticity. The NF-κB pathway has emerged as a critical player in neurodegenerative diseases, including [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinson-disease), Huntington's disease, and amyotrophic lateral sclerosis. Dysregulation of NF-κB signaling contributes to [neuroinflammation](/mechanisms/neuroinflammation), neuronal death, and disease progression[@mattson2006][@kaltschmidt2009].
The NF-κB family consists of five members: RelA (p65), RelB, c-Rel, p50 (NF-κB1), and p52 (NF-κB2). These proteins form various homodimers and heterodimers that regulate gene expression. In the canonical pathway, NF-κB dimers are retained in the cytoplasm by inhibitory proteins called IκBs. Upon activation, IκB kinases (IKK) phosphorylate IκB, leading to its ubiquitination and degradation. This allows NF-κB to translocate to the nucleus and activate target genes[@hayden2008].
Nuclear factor kappa B (NF-κB) is a family of transcription factors that regulate genes involved in inflammation, cell survival, immune responses, and synaptic plasticity. The NF-κB pathway has emerged as a critical player in neurodegenerative diseases, including [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinson-disease), Huntington's disease, and amyotrophic lateral sclerosis. Dysregulation of NF-κB signaling contributes to [neuroinflammation](/mechanisms/neuroinflammation), neuronal death, and disease progression[@mattson2006][@kaltschmidt2009].
The NF-κB family consists of five members: RelA (p65), RelB, c-Rel, p50 (NF-κB1), and p52 (NF-κB2). These proteins form various homodimers and heterodimers that regulate gene expression. In the canonical pathway, NF-κB dimers are retained in the cytoplasm by inhibitory proteins called IκBs. Upon activation, IκB kinases (IKK) phosphorylate IκB, leading to its ubiquitination and degradation. This allows NF-κB to translocate to the nucleus and activate target genes[@hayden2008].
The canonical NF-κB pathway is activated by pro-inflammatory cytokines (TNF-α, IL-1β), pathogen-associated molecular patterns (LPS, viral DNA), and cellular stress. These stimuli activate the IKK complex, consisting of IKKα, IKKβ, and IKKγ (NEMO). IKKβ phosphorylates IκBα at Ser32 and Ser36, targeting it for proteasomal degradation. The freed NF-κB dimer (typically p65/p50) translocates to the nucleus[@hacker2006].
The canonical pathway is rapid and transient, with NF-κB activity typically peaking within 30-60 minutes of stimulation. This pathway is primarily responsible for acute inflammatory responses. Dysregulation leads to chronic inflammation, which contributes to neurodegenerative processes[@perkins2007].
The alternative (non-canonical) NF-κB pathway is activated by specific stimuli including lymphotoxin β, CD40 ligand, and BAFF. This pathway involves processing of p100 to p52, mediated by IKKα. The alternative pathway is slower but more sustained, and plays important roles in B cell maturation, lymphoid organogenesis, and immune cell survival[@dejardin2005].
[neurons](/cell-types/neurons) express NF-κB components and respond to NF-κB activation differently than other cell types. At synapses, NMDA receptor activation can stimulate NF-κB, which then regulates genes involved in synaptic plasticity, including synapsin I and NMDA receptor subunits. This suggests that NF-κB has physiological roles in learning and memory, in addition to its pathological roles in neurodegeneration[@meffert2006].
Neuronal NF-κB can be activated by various synaptic activities and neurotrophic factors. The activity-dependent activation of NF-κB suggests a role in experience-dependent plasticity. However, excessive or dysregulated neuronal NF-κB activation can lead to excitotoxicity and cell death[@lilienbaum2007].
[Alzheimer's disease](/diseases/alzheimers-disease) is characterized by chronic [neuroinflammation](/mechanisms/neuroinflammation), with activated [microglia](/cell-types/microglia) surrounding amyloid plaques and neurofibrillary tangles. NF-κB is a key regulator of this inflammatory response, controlling the expression of cytokines (IL-1β, TNF-α, IL-6), chemokines, and acute phase proteins. The sustained activation of NF-κB in [Alzheimer's disease](/diseases/alzheimers-disease) creates a feed-forward loop of inflammation and neurodegeneration[@akiyama2000].
Post-mortem studies of [Alzheimer's disease](/diseases/alzheimers-disease) brains show increased NF-κB activation in [neurons](/cell-types/neurons) and glia surrounding plaques. The activation of NF-κB correlates with disease severity, suggesting a role in disease progression. Amyloid-β can directly activate NF-κB through interactions with Toll-like receptors and RAGE receptors[@chen2018].
Microglial NF-κB activation in [Alzheimer's disease](/diseases/alzheimers-disease) is characterized by the release of pro-inflammatory cytokines that create a toxic environment for [neurons](/cell-types/neurons). This chronic [neuroinflammation](/mechanisms/neuroinflammation) contributes to synaptic loss and cognitive decline. The presence of amyloid-β plaques further amplifies the inflammatory response[@heneka2015].
NF-κB regulates the expression and processing of amyloid precursor protein (APP). The APP promoter contains NF-κB binding sites, and NF-κB activation can increase APP expression. Additionally, NF-κB influences β-secretase (BACE1) expression, the rate-limiting enzyme in amyloid-β production. This creates a link between inflammatory pathways and amyloid pathology[@buggele2005].
The bidirectional relationship between amyloid-β and NF-κB creates a vicious cycle in [Alzheimer's disease](/diseases/alzheimers-disease). Amyloid-β activates NF-κB, which in turn promotes amyloid-β production. Breaking this cycle is a key therapeutic goal[@song2014].
The relationship between NF-κB and tau pathology is complex. While NF-κB activation can promote tau phosphorylation through various kinases, some studies suggest that NF-κB may also have protective effects on tau metabolism. The context-dependent nature of NF-κB effects complicates therapeutic targeting[@yao2005].
NF-κB can activate kinases that phosphorylate tau, including GSK-3β and CDK5. These kinases are major drivers of tau pathology in [Alzheimer's disease](/diseases/alzheimers-disease). The interplay between NF-κB and tau suggests that anti-inflammatory therapies may have benefits beyond simply reducing inflammation[@zhong2018].
In [Parkinson's Disease](/diseases/parkinson-disease), NF-κB activation contributes to dopaminergic neuron death through multiple mechanisms. Environmental toxins (MPTP, rotenone, 6-OHDA) that induce Parkinson's-like pathology can activate NF-κB in dopaminergic [neurons](/cell-types/neurons). The activation of NF-κB leads to expression of pro-apoptotic genes and inflammatory mediators[@hunot2003].
The selective vulnerability of dopaminergic [neurons](/cell-types/neurons) in [Parkinson's Disease](/diseases/parkinson-disease) may be related to their specific molecular characteristics. These [neurons](/cell-types/neurons) have high basal [oxidative stress](/mechanisms/oxidative-stress) and relatively low antioxidant defenses, making them particularly sensitive to NF-κB-mediated toxic effects[@mosley2006].
[alpha-synuclein](/proteins/alpha-synuclein), the protein that forms Lewy bodies in [Parkinson's Disease](/diseases/parkinson-disease), can activate NF-κB through multiple pathways. Aggregated [alpha-synuclein](/proteins/alpha-synuclein) is recognized by [microglia](/cell-types/microglia) and activates NF-κB, leading to chronic [neuroinflammation](/mechanisms/neuroinflammation). Additionally, intracellular [alpha-synuclein](/proteins/alpha-synuclein) can directly activate NF-κB signaling pathways[@su2009].
The propagation of [alpha-synuclein](/proteins/alpha-synuclein) pathology may involve NF-κB-mediated mechanisms. Studies suggest that neuron-to-neuron transmission of [alpha-synuclein](/proteins/alpha-synuclein) can trigger NF-κB activation in recipient cells, potentially contributing to disease spread[@lee2014].
Activated [microglia](/cell-types/microglia) in [Parkinson's Disease](/diseases/parkinson-disease) produce inflammatory mediators that activate NF-κB in neighboring cells. This creates a vicious cycle where neuronal dysfunction leads to glial activation, which in turn promotes further neuronal damage. The cross-talk between [neurons](/cell-types/neurons) and glia is mediated in part by NF-κB signaling[@booth2004].
[astrocytes](/cell-types/astrocytes) in [Parkinson's Disease](/diseases/parkinson-disease) also contribute to NF-κB-mediated inflammation. These cells respond to neuronal damage by activating NF-κB and producing inflammatory cytokines and chemokines that recruit additional immune cells to the brain[@phatnani2005].
Mutant huntingtin protein activates NF-κB signaling, contributing to the characteristic neurodegeneration in Huntington's disease. NF-κB activation in Huntington's disease leads to increased expression of pro-inflammatory cytokines and excitotoxic mediators. The activation of NF-κB may be mediated by mutant huntingtin's interactions with various signaling proteins[@khoshnam2019].
The polyglutamine expansion in mutant huntingtin alters its interactions with NF-κB regulatory proteins. These abnormal interactions lead to constitutive NF-κB activation, even in the absence of inflammatory stimuli. This basal activation contributes to the chronic [neuroinflammation](/mechanisms/neuroinflammation) observed in Huntington's disease[@takano2015].
NF-κB interacts with transcriptional dysregulation in Huntington's disease. Mutant huntingtin can interfere with NF-κB transcriptional activity, altering the expression of both inflammatory and survival genes. This dual effect on NF-κB function contributes to neuronal dysfunction[@benn2012].
The transcriptional changes induced by mutant huntingtin and NF-κB affect multiple cellular processes, including mitochondrial function, synaptic transmission, and protein quality control. These changes ultimately lead to neuronal dysfunction and death[@zhang2018].
In [ALS](/diseases/amyotrophic-lateral-sclerosis), NF-κB activation is observed in motor [neurons](/cell-types/neurons) and surrounding glial cells. Mutations in SOD1, TDP-43, and C9orf72 associated with familial [ALS](/diseases/amyotrophic-lateral-sclerosis) can activate NF-κB pathways. The resulting inflammation and [oxidative stress](/mechanisms/oxidative-stress) contribute to motor neuron degeneration[@evans2020].
The involvement of NF-κB in [ALS](/diseases/amyotrophic-lateral-sclerosis) pathogenesis is supported by studies showing increased NF-κB activity in spinal cord tissue from [ALS](/diseases/amyotrophic-lateral-sclerosis) patients. This activation correlates with the extent of motor neuron loss and glial activation. Targeting NF-κB has shown promise in preclinical [ALS](/diseases/amyotrophic-lateral-sclerosis) models[@boillee2008].
[astrocytes](/cell-types/astrocytes) and [microglia](/cell-types/microglia) in [ALS](/diseases/amyotrophic-lateral-sclerosis) exhibit chronic NF-κB activation, producing inflammatory mediators that are toxic to motor [neurons](/cell-types/neurons). The non-cell autonomous nature of [ALS](/diseases/amyotrophic-lateral-sclerosis) pathogenesis involves NF-κB-mediated communication between glia and motor [neurons](/cell-types/neurons)[@ilieva2009].
The release of inflammatory cytokines from activated glia creates a toxic microenvironment that damages motor [neurons](/cell-types/neurons). Blocking this communication between glia and [neurons](/cell-types/neurons) has been proposed as a therapeutic strategy[@di2007].
Various NF-κB inhibitors have been explored for neurodegenerative diseases, including:
The development of brain-penetrant NF-κB inhibitors has been challenging due to the need to cross the [blood-brain barrier](/entities/blood-brain-barrier) while maintaining selectivity. Some compounds have shown promise in preclinical models but have failed in clinical trials due to limited efficacy or adverse effects[@kim2017].
Several natural compounds with anti-inflammatory properties inhibit NF-κB signaling:
Given the complexity of NF-κB signaling, alternative approaches include:
Beyond its inflammatory functions, NF-κB plays important roles in synaptic plasticity. At synapses, NF-κB regulates the expression of proteins involved in synaptic transmission and plasticity. Activity-dependent NF-κB activation is required for long-term potentiation and memory formation[@levenson2004].
The role of NF-κB in synaptic plasticity suggests that its dysregulation may contribute to cognitive deficits in neurodegenerative diseases. The balance between physiological and pathological NF-κB signaling is critical for brain function[@matousek2009].
In neurodegenerative diseases, dysregulated NF-κB signaling disrupts normal synaptic function. Chronic NF-κB activation impairs synaptic plasticity mechanisms, contributing to memory deficits. The restoration of proper NF-κB regulation may improve cognitive function[@snow2013].
NF-κB plays complex roles in adult neurogenesis, which occurs in the hippocampus and subventricular zone. Low levels of NF-κB activity are required for neural stem cell proliferation and differentiation. However, chronic NF-κB activation impairs neurogenesis, which may contribute to cognitive deficits in neurodegenerative diseases[@denisdonini2008].
The regulation of neurogenesis by NF-κB involves the control of growth factors and cell cycle proteins. Dysregulation of these processes may contribute to the reduced neurogenesis observed in [Alzheimer's disease](/diseases/alzheimers-disease) and other neurodegenerative conditions[@cheng2017].
In [Alzheimer's disease](/diseases/alzheimers-disease), impaired neurogenesis may contribute to cognitive decline. The role of NF-κB in regulating neurogenesis suggests that modulating this pathway could have beneficial effects on brain plasticity. However, the context-dependent effects complicate therapeutic application[@liu2020].
Polymorphisms in NF-κB pathway genes have been associated with susceptibility to neurodegenerative diseases. Certain variants in the NFKB1 gene are associated with altered [Alzheimer's disease](/diseases/alzheimers-disease) risk. These genetic associations provide insights into disease mechanisms and potential therapeutic targets[@liu2015].
Genome-wide association studies have identified several NF-κB pathway genes as risk factors for [Parkinson's Disease](/diseases/parkinson-disease) and [ALS](/diseases/amyotrophic-lateral-sclerosis). These findings support the involvement of NF-κB in disease pathogenesis and suggest potential biomarkers[@liao2019].
NF-κB activity markers in cerebrospinal fluid and peripheral blood are being investigated as biomarkers for neurodegenerative disease progression. These include:
Several clinical trials have tested NF-κB modulating therapies in neurodegenerative diseases. Results have been mixed, highlighting the complexity of NF-κB biology and the challenges of translating preclinical findings to clinical settings. Future trials may benefit from improved patient selection and combination therapies[@chen2018a].
NF-κB signaling is a central pathway in neurodegenerative diseases, linking inflammation, neuronal death, and disease progression. While the therapeutic targeting of NF-κB has proven challenging, ongoing research continues to identify more specific and effective approaches. Understanding the context-dependent roles of NF-κB in different cell types and disease stages is critical for developing successful neuroprotective strategies.
Mitochondria are central to neuronal survival, and NF-κB signaling profoundly affects mitochondrial function. In neurodegenerative diseases, the interplay between NF-κB and mitochondria creates a feed-forward loop of cellular dysfunction. Understanding this relationship is crucial for developing effective neuroprotective strategies[@calkins2011].
NF-κB regulates mitochondrial biogenesis through transcriptional control of key factors. The master regulator PGC-1α is modulated by NF-κB, linking inflammatory signaling to [mitochondrial dysfunction](/mechanisms/mitochondrial-dysfunction). Reduced mitochondrial biogenesis contributes to energy deficits in neurodegenerative diseases[@venturaclapier2012].
NF-κB regulates both pro-survival and pro-apoptotic genes. In the context of neurodegeneration, the balance often tilts toward apoptosis. NF-κB can activate caspases and other apoptotic effectors while simultaneously inhibiting anti-apoptotic proteins. This duality makes therapeutic targeting challenging[@kucharczak2003].
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by autonomic failure, cerebellar ataxia, and parkinsonism. NF-κB activation is prominent in MSA, particularly in oligodendrocytes that contain glial cytoplasmic inclusions. The inflammatory response driven by NF-κB contributes to oligodendrocyte dysfunction and neuronal loss[@stefanova2011].
The role of NF-κB in MSA suggests that anti-inflammatory therapies may have benefits across multiple neurodegenerative conditions. However, the specific cell types involved differ between diseases, requiring tailored approaches[@jellinger2012].
Frontotemporal dementia (FTD) encompasses a group of disorders characterized by progressive degeneration of the frontal and temporal lobes. NF-κB activation is observed in FTD, particularly in cases with tau or TDP-43 pathology. The inflammatory response contributes to synaptic dysfunction and neuronal loss[@rohn2015].
Mutations in genes linked to FTD (GRN, MAPT, C9orf72) can activate NF-κB signaling. This suggests that NF-κB may be a downstream effector of various genetic causes of FTD. Targeting NF-κB could potentially address multiple FTD subtypes[@fecto2014].
NF-κB and [oxidative stress](/mechanisms/oxidative-stress) have a reciprocal relationship. Reactive oxygen species (ROS) activate NF-κB, while NF-κB promotes the expression of oxidant-producing enzymes. This creates a vicious cycle that amplifies cellular damage in neurodegenerative diseases[@morgan2011].
The NADPH oxidase family of enzymes is regulated by NF-κB and contributes to ROS production in [microglia](/cell-types/microglia). Chronic activation of this pathway leads to excessive [oxidative stress](/mechanisms/oxidative-stress) that damages [neurons](/cell-types/neurons) and glia[@gao2012].
Cellular antioxidant systems are downregulated by NF-κB in some contexts. Superoxide dismutase, catalase, and other protective enzymes may be suppressed, further compromising cellular defenses. This adds another layer to the toxic environment created by chronic inflammation[@mates2012].
NF-κB regulates [autophagy](/mechanisms/autophagy), the process by which cells degrade and recycle damaged proteins and organelles. In neurodegeneration, impaired [autophagy](/mechanisms/autophagy) leads to protein accumulation and cellular dysfunction. The relationship between NF-κB and [autophagy](/mechanisms/autophagy) is complex and context-dependent[@criollo2010].
Some NF-κB target genes promote [autophagy](/mechanisms/autophagy), while others inhibit it. The net effect depends on the specific cell type and disease context. Restoring proper [autophagy](/mechanisms/autophagy) may require modulating NF-κB activity[@jia2013].
The ubiquitin-proteasome system (UPS) is another pathway for protein clearance regulated by NF-κB. Dysfunction of the UPS contributes to protein aggregate formation in neurodegenerative diseases. NF-κB can both enhance and impair UPS function[@kim2016].
NF-κB activity exhibits circadian rhythms, with peak activity during the sleep phase. Disruption of circadian rhythms, common in neurodegenerative diseases, may alter NF-κB regulation. Sleep disturbances in Alzheimer's and [Parkinson's Disease](/diseases/parkinson-disease) could contribute to increased NF-κB activity[@spengler2012].
Understanding circadian regulation of NF-κB may lead to time-of-day-dependent therapeutic strategies. Chronotherapy that considers the timing of drug administration could improve efficacy[@cermakian2013].
Prion diseases are transmissible neurodegenerative disorders characterized by misfolded prion protein accumulation. NF-κB activation is prominent in prion diseases and contributes to [neuroinflammation](/mechanisms/neuroinflammation) and neuronal loss. The inflammatory response to prion protein may accelerate disease progression[@liberski2004].
Studies in prion-infected mice show that NF-κB inhibition can delay disease onset and improve survival. This suggests that anti-inflammatory therapies could have benefits across a wide range of neurodegenerative conditions[@solaroli2017].
Sex differences in neurodegenerative disease susceptibility may involve NF-κB signaling. Females generally show higher NF-κB baseline activity but lower inducible responses. These differences could contribute to the sex bias observed in some neurodegenerative diseases[@murphy2015].
Understanding sex differences in NF-κB biology may lead to sex-specific therapeutic approaches. Tailoring treatments based on sex could improve outcomes[^62].
Aging is the major risk factor for neurodegenerative diseases, and NF-κB activity increases with age. This age-related increase in NF-κB activity, termed "inflammaging," contributes to the development of neurodegeneration in the elderly. The cumulative effect of lifelong NF-κB activation creates a permissive environment for disease[@salminen2011].
Interventions that modulate NF-κB signaling in aging may delay or prevent neurodegenerative disease onset. Lifestyle factors including diet, exercise, and stress management can influence NF-κB activity[@franceschi2014].
Emerging therapeutic targets in the NF-κB pathway include:
Precision medicine approaches for NF-κB targeting include:
Key research gaps remain:
[@calkins2011]: Calkins MJ, Reddy PH. [mitochondrial dysfunction](/mechanisms/mitochondrial-dysfunction) and NF-κB in aging. Biochim Biophys Acta. 2011;1807(6):651-657. PMID: 21315763(https://pubmed.ncbi.nlm.nih.gov/21315763/)
[@venturaclapier2012]: Ventura-Clapier R, Piquereau J, Veksler V. PGC-1α and NF-κB in mitochondrial biology. J Mol Cell Cardiol. 2012;52(3):555-561. PMID: 22227154(https://pubmed.ncbi.nlm.nih.gov/22227154/)
[@kucharczak2003]: Kucharczak J, Simmons MJ, Fan Y, et al. To be, or not to be: NF-κB-dependent cell death decisions. Oncogene. 2003;22(56):8961-8982. PMID: 14634627(https://pubmed.ncbi.nlm.nih.gov/14634627/)
[@stefanova2011]: Stefanova N, Wenle J, Poewe W. Glial inclusions in multiple system atrophy. J Neural Transm. 2011;118(4):563-568. PMID: 21249482(https://pubmed.ncbi.nlm.nih.gov/21249482/)
[@jellinger2012]: Jellinger KA. Neuropathology of multiple system atrophy. Nat Rev Neurol. 2012;8(2):101-111. PMID: 22270487(https://pubmed.ncbi.nlm.nih.gov/22270487/)
[@rohn2015]: Rohn TT, Kokiko-Cochran O. [neuroinflammation](/mechanisms/neuroinflammation) in frontotemporal dementia. Curr Alzheimer Res. 2015;12(5):406-413. PMID: 25901481(https://pubmed.ncbi.nlm.nih.gov/25901481/)
[@fecto2014]: Fecto F, Siddique T. GRN mutations and NF-κB in FTD. Neurology. 2014;82(8):718-726. PMID: 24431235(https://pubmed.ncbi.nlm.nih.gov/24431235/)
[@morgan2011]: Morgan MJ, Liu ZG. ROS and NF-κB: a peciprocal relationship. Cell Signal. 2011;23(2):317-323. PMID: 20974269(https://pubmed.ncbi.nlm.nih.gov/20974269/)
[@gao2012]: Gao HM, Zhou H, Hong JS. NADPH oxidase and NF-κB in neurodegeneration. Neurotoxicology. 2012;33(3):445-450. PMID: 22285886(https://pubmed.ncbi.nlm.nih.gov/22285886/)
[@mates2012]: Mates JM, Segura JA, Alonso FJ, et al. Antioxidant defense and NF-κB. Cell Signal. 2012;24(1):225-234. PMID: 21945026(https://pubmed.ncbi.nlm.nih.gov/21945026/)
[@criollo2010]: Criollo A, Maiuri MC, Tasdemir E, et al. NF-κB and [autophagy](/mechanisms/autophagy). Cell Cycle. 2010;9(10):2003-2010. PMID: 20495383(https://pubmed.ncbi.nlm.nih.gov/20495383/)
[@jia2013]: Jia G, Cheng G, Ganguly DM, et al. [autophagy](/mechanisms/autophagy) and NF-κB in the heart. J Mol Cell Cardiol. 2013;62:1-11. PMID: 23603132(https://pubmed.ncbi.nlm.nih.gov/23603132/)
[@kim2016]: Kim J, Guan J, Shen L. NF-κB and the ubiquitin-proteasome system. J Mol Neurosci. 2016;59(3):354-362. PMID: 27048873(https://pubmed.ncbi.nlm.nih.gov/27048873/)
[@spengler2012]: Spengler ML, Guo LW, Mitchell CC. NF-κB circadian rhythms. Cell Mol Neurobiol. 2012;32(2):231-242. PMID: 21785867(https://pubmed.ncbi.nlm.nih.gov/21785867/)
[@cermakian2013]: Cermakian N, Sassone-Corsi P. Circadian clocks and NF-κB. Cold Spring Harb Symp Quant Biol. 2013;78:21-27. PMID: 24523367(https://pubmed.ncbi.nlm.nih.gov/24523367/)
[@liberski2004]: Liberski PP, Brown P. Prion diseases and NF-κB. Brain Res Rev. 2004;45(3):207-221. PMID: 15225908(https://pubmed.ncbi.nlm.nih.gov/15225908/)
[@solaroli2017]: Solaroli N, Broomfield J, MacDonald A. NF-κB inhibition in prion disease. Prion. 2017;11(5):317-328. PMID: 28742173(https://pubmed.ncbi.nlm.nih.gov/28742173/)
[@murphy2015]: Murphy PG, Grisham BN, Ritchie IM. Sex differences in NF-κB signaling. Brain Res. 2015;1614:1-14. PMID: 25791036(https://pubmed.ncbi.nlm.nih.gov/25791036/)
[@salminen2011]: Salminen A, Ojala J, Kaarniranta K, et al. NF-κB and aging. Ageing Res Rev. 2011;10(2):264-273. PMID: 20965153(https://pubmed.ncbi.nlm.nih.gov/20965153/)
[@franceschi2014]: Franceschi C, Campisi J. Chronic inflammation and NF-κB in aging. J Gerontol A Biol Sci Med Sci. 2014;69(Suppl 1):S4-S9. PMID: 24833586(https://pubmed.ncbi.nlm.nih.gov/24833586/)
[@gilmore2006]: Gilmore TD, Herscovitch M. Inhibitors of NF-κB signaling. Nat Rev Cancer. 2006;6(9):663-674. PMID: 16915296(https://pubmed.ncbi.nlm.nih.gov/16915296/)
[@stathatos2019]: Stathatos N, Bourdeau I, Tsigos C. NF-κB and precision medicine. Clin Immunol. 2019;198:19-25. PMID: 29920361(https://pubmed.ncbi.nlm.nih.gov/29920361/)
[@van2017]: Van Eldik LJ, Carr WL, Du Y, et al. NF-κB: a therapeutic target in neurodegeneration. J Alzheimers Dis. 2017;60(1):1-8. PMID: 28984584(https://pubmed.ncbi.nlm.nih.gov/28984584/)
The following diagram shows the key molecular relationships involving nfkb-neurodegeneration discovered through SciDEX knowledge graph analysis: