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.
| Property |
Value |
| Symbol |
TNFRSF1A |
| Full Name |
Tumor necrosis factor receptor superfamily member 1A |
| Chromosomal Location |
12p13.31 |
| NCBI Gene ID |
7132 |
| OMIM |
191190 |
| Ensembl |
ENSG00000082258 |
| UniProt |
P19438 |
TNFRSF1A encodes TNFR1, a receptor that plays central roles in inflammation and cell survival:
- NF-κB pathway: TNFR1 activation leads to IKK complex activation, resulting in NF-κB nuclear translocation and pro-inflammatory gene expression
- MAPK pathways: JNK and p38 MAPK activation mediate stress responses
- Caspase-8 activation: Can initiate apoptosis under certain conditions
- Pro-inflammatory cytokine response
- Cell survival and death decisions
- Immune cell activation
- Acute phase response
TNFRSF1A is expressed in:
In the brain:
- High expression in cortex, hippocampus, basal ganglia
- Upregulated in response to injury or disease
TNF-α/TNFR1 signaling is a key driver of neuroinflammation in neurodegenerative diseases.
- Elevated TNFR1 expression in AD brain tissue correlates with disease severity
- 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
Mechanism: Aβ → TNFR1 activation → NF-κB → IL-1β, TNF-α production → chronic neuroinflammation → synaptic loss
- TNFR1 is upregulated in substantia nigra pars compacta of PD patients
- Mediates microglial activation and dopaminergic neuron death
- Contributes to neuroinflammation in the Substantia nigra
Mechanism: α-synuclein aggregation → microglial activation → TNF-α release → TNFR1 on neurons → apoptosis
- TNF-α signaling is hyperactive in HD
- TNFR1 mediates excitotoxic cell death
- Contributes to striatal neuron degeneration
- Elevated TNF-α in CSF and serum of ALS patients
- TNFR1 contributes to motor neuron death
- Microglial activation mediated by TNFR1 drives disease progression
flowchart TD
ATNF-α R["elease"] --> B["Microglial Activation"]
A --> C["Neuronal Stress"]
B --> D{"TNFR1 Activation"}
C --> D
D --> ENF-κB P["athway"]
D --> F["MAPK Pathway"]
D --> G["Caspase Activation"]
E --> H["Pro-inflammatory Genes"]
E --> IIL-1β, IL-6, TNF-α
F --> J["Stress Response"]
F --> K["Apoptosis"]
G --> K
H --> L["Chronic Neuroinflammation"]
L --> M["Synaptic Dysfunction"]
M --> N["Neuronal Death"]
K --> N
style A fill:#fff9c4
style D fill:#ffcc80
style L fill:#ffcdd2
style N fill:#ef9a9a
Targeting TNFR1 signaling offers therapeutic potential:
- TNFR1 antagonists: Decoy receptors, neutralizing antibodies
- NF-κB inhibitors: Reduce downstream inflammatory response
- Anti-inflammatory agents: Minimize microglial activation
- Natural compounds: Curcumin, resveratrol modulate TNFR1 pathways