TNFRSF1A Gene
Overview <table class="infobox infobox-gene">
TNFRSF1A (Tumor Necrosis Factor Receptor Superfamily Member 1A) encodes the TNFR1 protein, a cell surface receptor for tumor necrosis factor-alpha (TNF-α). This gene is critical for inflammatory signaling and has been implicated in neurodegenerative diseases. [@sharif2022][@cheng2021]
Normal Function ...
TNFRSF1A Gene
Overview <table class="infobox infobox-gene">
TNFRSF1A (Tumor Necrosis Factor Receptor Superfamily Member 1A) encodes the TNFR1 protein, a cell surface receptor for tumor necrosis factor-alpha (TNF-α). This gene is critical for inflammatory signaling and has been implicated in neurodegenerative diseases. [@sharif2022][@cheng2021]
Normal Function TNFRSF1A encodes TNFR1, a receptor that plays central roles in inflammation and cell survival:
Signaling Pathways
[NF-κB](/entities/nf-kb) pathway : TNFR1 activation leads to IKK complex activation, resulting in NF-κB nuclear translocation and pro-inflammatory gene expression [@chen2017]MAPK pathways : JNK and p38 MAPK activation mediate stress responsesCaspase-8 activation : Can initiate apoptosis under certain conditionsCellular Functions
Pro-inflammatory cytokine response
Cell survival and death decisions
Immune cell activation
Acute phase response
Expression Pattern TNFRSF1A is expressed in:
Brain: [neurons](/entities/neurons), [astrocytes](/entities/astrocytes), [microglia](/cell-types/microglia-neuroinflammation)
Immune cells: macrophages, T cells
Various peripheral tissues
In the brain:
High expression in [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), basal ganglia
Upregulated in response to injury or disease
Role in Neurodegeneration TNF-α/TNFR1 signaling is a key driver of neuroinflammation in neurodegenerative diseases.
Alzheimer's Disease (AD)
Elevated TNFR1 expression in AD brain tissue correlates with disease severity [@zhao2018]
[Amyloid-beta](/proteins/amyloid-beta) oligomers induce TNFR1 upregulation on neurons and glia
TNFR1 mediates amyloid-beta induced neurotoxicity through NF-κB
Genetic variants in TNFRSF1A may modify AD risk [@busso2009]
Mechanism : Aβ → TNFR1 activation → NF-κB → IL-1β, TNF-α production → chronic neuroinflammation → synaptic loss
Parkinson's Disease (PD)
TNFR1 is upregulated in substantia nigra pars compacta of PD patients [@boka2014]
Mediates microglial activation and dopaminergic neuron death
Contributes to neuroinflammation in the Substantia nigra
Mechanism : [α-synuclein](/proteins/alpha-synuclein) aggregation → microglial activation → TNF-α release → TNFR1 on neurons → apoptosis
Huntington's Disease (HD)
TNF-α signaling is hyperactive in HD
TNFR1 mediates excitotoxic cell death [@fontaine2000]
Contributes to striatal neuron degeneration
Amyotrophic Lateral Sclerosis (ALS)
Elevated TNF-α in CSF and serum of ALS patients
TNFR1 contributes to motor neuron death
Microglial activation mediated by TNFR1 drives disease progression
Mermaid Diagram: TNFR1 Signaling in Neurodegeneration
Therapeutic Implications Targeting TNFR1 signaling offers therapeutic potential:
TNFR1 antagonists : Decoy receptors, neutralizing antibodiesNF-κB inhibitors : Reduce downstream inflammatory responseAnti-inflammatory agents : Minimize microglial activationNatural compounds : Curcumin, resveratrol modulate TNFR1 pathwaysSee Also
[TNFR1 Protein](/proteins/tnfr1)
[TNF Alpha](/proteins/tnf-alpha)
[Neuroinflammation](/mechanisms/neuroinflammation)
[Alzheimer's Disease](/diseases/alzinhers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[NF-κB Signaling](/mechanisms/nf-kb-signaling-neuroinflammation)
External Links
[NCBI Gene 7132](https://www.ncbi.nlm.nih.gov/gene/7132)
[OMIM 191190](https://www.omim.org/entry/191190)
[Ensembl ENSG00000082258](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000082258)
[UniProt P19438](https://www.uniprot.org/uniprot/P19438)
References
[Sharif et al., TNFRSF1A in neurodegeneration (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35678912/)
[Cheng et al., TNFR1 in Parkinson's disease (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/33448256/)
[Chen et al., NF-κB in neuroinflammation (2017) (2017)](https://pubmed.ncbi.nlm.nih.gov/28336943/)
[Zhao et al., TNFR1 elevation in AD brain (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29526534/)
[Busso et al., TNF genetic variants and AD risk (2009) (2009)](https://pubmed.ncbi.nlm.nih.gov/19356478/)
[Boka et al., TNFR1 in Parkinson's disease substantia nigra (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/25040066/)
[Fontaine et al., TNF signaling in Huntington's disease (2000) (2000)](https://pubmed.ncbi.nlm.nih.gov/10657863/)
Pathway Diagram The following diagram shows the key molecular relationships involving TNFRSF1A Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
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