FAS (Fas cell surface death receptor) is a member of the TNF receptor superfamily that plays a critical role in the extrinsic apoptosis pathway. It is widely expressed in the nervous system and contributes to neuronal death in various neurodegenerative diseases.
FAS (also known as CD95 or APO-1) is a cell surface receptor that triggers apoptosis upon binding with its ligand FASLG. It is a type I transmembrane protein containing death domains that initiate caspase-8 activation.
| Fas Cell Surface Death Receptor |
|---|
| Gene Symbol | FAS |
| Full Name | Fas Cell Surface Death Receptor |
| Chromosome | 10q23.31 |
| NCBI Gene ID | 3558 |
| OMIM | 134637 |
| Ensembl ID | ENSG00000026103 |
| UniProt ID | P01375 |
FAS mediates the extrinsic apoptosis pathway:
- Ligand binding: FASL (Fas ligand) binds to FAS receptor trimer
- Death domain recruitment: FADD and procaspase-8 are recruited
- DISC formation: Death-inducing signaling complex (DISC) forms
- Caspase-8 activation: Activated caspase-8 initiates apoptosis
¶ Type I and Type II Cells
- Type I cells: High DISC formation, direct caspase-3 activation
- Type II cells: Require mitochondrial amplification for apoptosis
FAS contributes to AD pathogenesis:
- Neuronal death: FAS-mediated apoptosis in affected brain regions
- Aβ toxicity: Amyloid-beta increases FAS expression
- Synaptic loss: FAS signaling contributes to synaptic dysfunction
- Neuroinflammation: FAS in glial cells promotes inflammation
In PD, FAS mediates dopaminergic neuron death:
- Nigericin-induced toxicity: Increases FAS signaling
- α-Synuclein interaction: May be modulated by alpha-synuclein
- Oxidative stress: FAS activation by reactive oxygen species
FAS is implicated in motor neuron disease:
- Motor neuron death: FAS-mediated apoptosis
- Glial cell involvement: Astrocyte and microglia express FAS
- Neuromuscular junction: Contributes to denervation
¶ Stroke and TBI
FAS contributes to acute brain injury:
- Ischemic stroke: FAS-mediated neuronal death
- Traumatic brain injury: Secondary neuronal apoptosis
FAS/FASL pathway inhibitors are investigated:
| Agent |
Mechanism |
Status |
Disease |
| FAS siRNA |
Gene silencing |
Research |
Stroke |
| Anti-FASL antibodies |
Block ligand |
Preclinical |
Neuroprotection |
| FADD dominant negative |
Block DISC |
Research |
TBI |
| Disease |
Role |
Evidence |
| Alzheimer's Disease |
Neuronal apoptosis |
Elevated FAS in AD brain |
| Parkinson's Disease |
Dopaminergic death |
FAS activation in PD models |
| ALS |
Motor neuron death |
FAS-mediated apoptosis |
| Stroke |
Ischemic injury |
FAS knockout protective |
FAS is expressed in brain tissue:
- High expression in cerebral cortex
- Expressed in neurons and glia
- Upregulated in disease states
- FAS in neurodegeneration (2021)
- FAS and Alzheimer's disease (2020)
- FAS-mediated apoptosis in PD (2019)
- FAS in ALS pathogenesis (2022)
- FAS and neuroinflammation (2021)
- Therapeutic targeting of FAS (2020)
- FAS in stroke (2019)
- FAS and synaptic dysfunction (2022)