TNFRSF1A (Tumor Necrosis Factor Receptor Superfamily Member 1A), also known as TNFR1 or p55, is a member of the TNF receptor superfamily that plays a critical role in inflammation, cell survival, and apoptosis. It is widely expressed in the nervous system and contributes to neuroinflammation and neuronal death in neurodegenerative diseases.
TNFR1 is a type I transmembrane receptor that can initiate both pro-inflammatory and pro-apoptotic signaling cascades. It is one of the primary receptors for TNF-α, a key cytokine in neuroinflammation.
| TNF Receptor Superfamily Member 1A | |
|---|---|
| Gene Symbol | TNFRSF1A |
| Full Name | TNF Receptor Superfamily Member 1A |
| Chromosome | 12p13.31 |
| NCBI Gene ID | 7132 |
| OMIM | 191191 |
| Ensembl ID | ENSG00000121440 |
| UniProt ID | P19438 |
TNFR1 mediates both inflammatory and apoptotic signaling:
NF-κB pathway (pro-survival/inflammatory):
MAPK pathways:
Apoptosis pathway (when NF-κB is inhibited):
TNFR1 contributes to AD pathogenesis:
In PD, TNFR1 contributes to:
TNFR1 is implicated in motor neuron disease:
TNFR1 plays a key role in demyelination:
TNFR1 inhibitors are investigated for neuroprotection:
| Agent | Mechanism | Status | Disease |
|---|---|---|---|
| Etanercept | Decoy receptor | Clinical (autoimmune) | MS, AD (trial) |
| Infliximab | Anti-TNF antibody | Research | Neuroinflammation |
| Small molecule inhibitors | Block signaling | Preclinical | PD |
| Disease | Role | Evidence |
|---|---|---|
| Alzheimer's Disease | Neuroinflammation | Elevated TNFR1 in AD brain |
| Parkinson's Disease | Dopaminergic death | TNFR1 in SN |
| ALS | Motor neuron death | TNFR1-mediated toxicity |
| MS | Demyelination | TNFR1 in lesions |
TNFR1 is widely expressed in the nervous system: