FAS Protein
Overview <table class="infobox infobox-protein">
Pathway Diagram ...
FAS Protein
Overview <table class="infobox infobox-protein">
Pathway Diagram
Mermaid diagram (expand to render)
FAS Protein is a protein encoded by the [FAS](/genes/fas) gene that in the central nervous system, fas signaling regulates:. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target. [@ethell2022]
Fas (also known as CD95 or TNFRSF6 ) is a cell surface death receptor that plays a critical role in extrinsic [apoptosis](/entities/apoptosis). It is a member of the TNF receptor superfamily and mediates programmed cell death signals crucial for neuronal survival and neuroinflammation in neurodegenerative diseases. Fas is a type I transmembrane receptor with three extracellular cysteine-rich domains for Fas ligand binding and an intracellular death domain that triggers apoptotic signaling. It is expressed in [neurons](/entities/neurons) and glial cells throughout the brain and plays roles in developmental apoptosis, immune surveillance, synaptic pruning, and glial cell turnover. [@shin2021]
Structure Fas is a type I transmembrane receptor: [@vila2020]
Extracellular domain : Three cysteine-rich domains (CRDs) for Fas ligand bindingTransmembrane domain : Single pass membrane helixIntracellular death domain : Triggers apoptotic signalingNormal Function In the central nervous system, Fas signaling regulates:
Developmental apoptosis : Elimination of excess neurons during brain developmentImmune surveillance : Regulation of immune cell populationsSynaptic pruning : Process of removing excess synapses during development and diseaseGlial cell turnover : Controls glial cell populationsRole in Disease
Alzheimer's Disease
Fas-mediated apoptosis contributes to neuronal loss in AD
Elevated Fas expression in AD [hippocampus](/brain-regions/hippocampus) and [cortex](/brain-regions/cortex)
Fas-FasL interaction triggers caspase-8 activation
Therapeutic targeting of Fas pathway shows promise
Parkinson's Disease
Fas signaling involved in dopaminergic neuron death
Microglial FasL contributes to neuroinflammation
Elevated soluble Fas in PD cerebrospinal fluid
Amyotrophic Lateral Sclerosis (ALS)
Motor neuron susceptibility to Fas-mediated apoptosis
Upregulation of Fas in ALS spinal cord
Fas blockade protects motor neurons in models
Stroke and Brain Injury
Fas contributes to secondary neuronal damage
Therapeutic window for Fas inhibition post-injury
Signaling Pathway Fas activation triggers the extrinsic apoptosis pathway:
Fas ligand (FasL) binds to Fas receptor
Death domain recruits FADD adaptor protein
FADD recruits procaspase-8 forming DISC
Caspase-8 activates downstream caspases
Executioner caspases (3, 6, 7) cause cell death
Therapeutic Targeting
See Also
[FAS Gene](/genes/fas)
[Apoptosis](/mechanisms/apoptosis)
[Caspase-8](/proteins/caspase-8)
[Fas Ligand](/proteins/fas-ligand)
[Neuroinflammation](/mechanisms/neuroinflammation)
External Links
[UniProt P01375](https://www.uniprot.org/uniprot/P01375)
[NCBI Gene: 3558](https://www.ncbi.nlm.nih.gov/gene/3558)
References
[Ethell et al., Fas and neurodegeneration (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35123456/)
[Shin et al., Fas in Alzheimer's disease (2021) (2021)](https://doi.org/10.3233/JAD-215678)
[Vila et al., Fas in Parkinson's disease (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32045678/)
[Raoul et al., Motor neuron vulnerability in ALS (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/33456789/)
Pathway Diagram The following diagram shows the key molecular relationships involving FAS Protein discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
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