FAS Gene

FAS Gene

Introduction

Pathway Diagram

```mermaid
flowchart TD
FAS_gene["FAS<br/>Gene"]
FAS_protein["FAS<br/>Protein"]
FOXO["FOXO<br/>Transcription Factor"]
AMBRA1["AMBRA1<br/>Autophagy Regulator"]

apoptosis["Apoptosis<br/>Cell Death"]
neurodegeneration["Neurodegeneration<br/>Disease Process"]
neuroinflammation["Neuroinflammation<br/>Immune Response"]

alzheimer["Alzheimer's<br/>Disease"]
als["ALS<br/>Disease"]
ms["Multiple<br/>Sclerosis"]

TNF["TNF<br/>Cytokine"]
IL6["IL6<br/>Cytokine"]
APOE["APOE<br/>Lipid Transport"]

inflammation["Chronic<br/>Inflammation"]
aging["Cellular<br/>Aging"]
senescence["Cellular<br/>Senescence"]

FOXO -->|"activates"| FAS_gene
AMBRA1 -->|"regulates"| FAS_protein
FAS_gene -->|"encodes"| FAS_protein

FAS_protein -->|"activates"| apoptosis
FAS_gene -->|"activates"| neurodegeneration
FAS_gene -->|"activates"| neuroinflammation

FAS_gene -->|"activates"| alzheimer
FAS_gene -->|"activates"| als
FAS_gene -->|"activates"| ms

FAS_gene -->|"activates"| TNF
FAS_gene -->|"activates"| IL6
FAS_gene -->|"interacts_with"| APOE

FAS_gene -->|"regulates"| inflammation
FAS_gene -->|"regulates"| aging
FAS_gene -->|"regulates"| senescence

apoptosis -->|"contributes_to"| neurodegeneration
neuroinflammation -->|"promotes"| neurodegeneration

style FAS_gene fill:#006494
style FAS_protein fill:#006494
style AMBRA1 fill:#4a1a6b
style FOXO fill:#4a1a6b
style apopto

FAS Gene

Introduction

Pathway Diagram

FAS (Fas cell surface death receptor) is a member of the TNF receptor superfamily that plays a critical role in the extrinsic [apoptosis](/entities/apoptosis) pathway. It is widely expressed in the nervous system and contributes to neuronal death in various neurodegenerative diseases.

Overview

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. [@fas2020]

<div class="infobox infobox-gene"> [@fasmediated2019]
<table> [@fas2022]
<tr><th colspan="2" style="background:#f0f0f0;">Fas Cell Surface Death Receptor</th></tr> [@fas2021a]
<tr><td><strong>Gene Symbol</strong></td><td>FAS</td></tr> [@therapeutic2020]
<tr><td><strong>Full Name</strong></td><td>Fas Cell Surface Death Receptor</td></tr> [@fas2019]
<tr><td><strong>Chromosome</strong></td><td>10q23.31</td></tr> [@fas2022a]
<tr><td><strong>NCBI Gene ID</strong></td><td>[3558](https://www.ncbi.nlm.nih.gov/gene/3558)</td></tr>
<tr><td><strong>OMIM</parameter><td>[134637](https://www.omim.org/entry/134637)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>[ENSG00000026103](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000026103)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P01375](https://www.uniprot.org/uniprot/P01375)</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/ami" style="color:#ef9a9a">AMI</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">451 edges</a></td>
</tr>
</table>
</div>

Molecular Mechanism

FAS mediates the extrinsic apoptosis pathway:

Activation Cascade

Type I and Type II Cells

• Type I cells: High DISC formation, direct caspase-3 activation
• Type II cells: Require mitochondrial amplification for apoptosis

Function in Neurodegeneration

Alzheimer's Disease

FAS contributes to AD pathogenesis:

• Neuronal death: FAS-mediated apoptosis in affected brain regions
• Aβ toxicity: [Amyloid-beta](/proteins/amyloid-beta) increases FAS expression
• Synaptic loss: FAS signaling contributes to synaptic dysfunction
• Neuroinflammation: FAS in glial cells promotes inflammation

Parkinson's Disease

In PD, FAS mediates dopaminergic neuron death:

• Nigericin-induced toxicity: Increases FAS signaling
• α-Synuclein interaction: May be modulated by [alpha-synuclein](/proteins/alpha-synuclein)
• Oxidative stress: FAS activation by [reactive oxygen species](/entities/reactive-oxygen-species)

ALS

FAS is implicated in motor neuron disease:

• Motor neuron death: FAS-mediated apoptosis
• Glial cell involvement: Astrocyte and [microglia](/cell-types/microglia-neuroinflammation) 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

Therapeutic Targeting

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 Associations

| 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 |

Expression

FAS is expressed in brain tissue:

• High expression in cerebral [cortex](/brain-regions/cortex)
• Expressed in [neurons](/entities/neurons) and glia
• Upregulated in disease states

See Also

• [FASLG Gene](/genes/fasl) - Fas ligand
• [FADD Gene](/genes/fadd) - FAS-associated death domain
• [CASP8 Gene](/genes/casp8) - Initiator caspase
• [Apoptosis Pathway](/entities/apoptosis-pathway)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [NCBI Gene: fas](https://www.ncbi.nlm.nih.gov/gene/)
• [PubMed: fas](https://pubmed.ncbi.nlm.nih.gov/?term=fas+neurodegeneration)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving FAS Gene discovered through SciDEX knowledge graph analysis: