FSP1/CoQ10 Axis as GPX4-Independent Neuroprotective Pathway
🧪 Overview
FSP1 generates CoQ10 to trap lipid peroxyl radicals at the plasma membrane, providing GPX4-independent protection. However, CoQ10 supplementation is implausible for acute post-CA injury (hours timeframe) due to limited brain penetration and primary mitochondrial localization. 'FSP1 inducer' (Nrf2 activators) activate hundreds of genes without FSP1 specificity. CoQ10 trials in cardiac arrest survivors showed no neurological benefit. FSP1 expression in brain microvascular endothelial cells is uncharacterized.
🧬 Mechanism
Curated pathway from expert analysis
flowchart TD
A["FSP1/FSHR1 Ferroptosis Suppressor<br/>NQO1-Like Enzyme"]
B["CoQ10 Regeneration<br/>NADPH-Dependent Ubiquinone Reduction"]
C["GPX4-Independent Ferroptosis Defense<br/>Lipid Peroxide Detoxification"]
D["Iron-Dependent Cell Death<br/>Ferroptosis Execution"]
E["GPX4 and FSP1 Dual Axis<br/>Robust Ferroptosis Barrier"]
F["FSP1 Knockdown<br/>Ferroptosis Vulnerability Increased"]
A --> B
B --> C
C --> E
D -.->|"induces"| F
E --> D
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style E fill:#1b5e20,stroke:#81c784,color:#81c784
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — FSP1
No curated PDB or AlphaFold mapping for FSP1 yet. Search RCSB →
💉 Clinical Trials
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for FSP1 (NQO1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
📊 Market Indicators
💾 Resource Usage
🔮 Predictions
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF CRISPR/Cas9-mediated FSP1 knockout iPSC-derived neurons are exposed to oxygen-glucose deprivation (OGD) for 90 min, THEN knockout cells will show ≥40% increase in cell death (PI staining) at 24h co | Significant increase in neuronal death following FSP1 knockout under OGD | — no observation — | pending | 0.45 |
| IF human brain microvascular endothelial cells (hBMVECs) are isolated from post-cardiac arrest patients within 24 hours and FSP1 protein expression is quantified by immunoblot, THEN endothelial FSP1 l | Positive correlation between endothelial FSP1 expression and neurological recovery | — no observation — | pending | 0.35 |
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesizer
| source | v1_phase_c_backfill |
| origin_type | debate_synthesizer |
| _schema_version | 1 |