TNFRSF1A Gene

Overview

TNFRSF1A Gene
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
Associated Diseases	ALS, Als, Alzheimer, Anxiety, Atherosclerosis
KG Connections	118 edges

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. ^{1TNFRSF1A in neurodegeneration (2022)2022 · PMID 35678912Open reference2TNFR1 in Parkinson's disease (2021)2021 · PMID 33448256Open reference}

Gene Information

Normal Function

TNFRSF1A encodes TNFR1, a receptor that plays central roles in inflammation and cell survival:

Signaling Pathways

• NF-κB pathway: TNFR1 activation leads to IKK complex activation, resulting in NF-κB nuclear translocation and pro-inflammatory gene expression ^{3NF-κB in neuroinflammation (2017)2017 · PMID 28336943Open reference}

• MAPK pathways: JNK and p38 MAPK activation mediate stress responses

• Caspase-8 activation: Can initiate apoptosis under certain conditions

Cellular Functions

• Pro-inflammatory cytokine response

• Cell survival and death decisions

• Immune cell activation

• Acute phase response

Expression Pattern

TNFRSF1A is expressed in:

• Brain: neurons, astrocytes, microglia

• Immune cells: macrophages, T cells

• Various peripheral tissues

In the brain:

• High expression in cortex, 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 ^{4TNFR1 elevation in AD brain (2018)2018 · PMID 29526534Open reference}

• 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 ^{5TNF genetic variants and AD risk (2009)2009 · PMID 19356478Open reference}

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 ^{6TNFR1 in Parkinson's disease substantia nigra (2014)2014 · PMID 25040066Open reference}

• 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

Huntington’s Disease (HD)

• TNF-α signaling is hyperactive in HD

• TNFR1 mediates excitotoxic cell death ^{7TNF signaling in Huntington's disease (2000)2000 · PMID 10657863Open reference}

• 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 antibodies

• NF-κB inhibitors: Reduce downstream inflammatory response

• Anti-inflammatory agents: Minimize microglial activation

• Natural compounds: Curcumin, resveratrol modulate TNFR1 pathways

See Also

• TNFR1 Protein

• TNF Alpha

• Neuroinflammation

• Alzheimer’s Disease

• Parkinson’s Disease

• NF-κB Signaling

External Links

• NCBI Gene 7132

• OMIM 191190

• Ensembl ENSG00000082258

• UniProt P19438