Pentose Phosphate Pathway Suppression Enables Ferroptosis Vulnerability
🧪 Overview
NADPH depletion from PPP inhibition creates ferroptosis susceptibility in vulnerable neurons. Neurodegeneration-associated metabolic stress suppresses the pentose phosphate pathway, reducing NADPH availability. Without adequate NADPH to regenerate reduced glutathione, GPX4 activity becomes insufficient to detoxify lipid peroxides, rendering neurons susceptible to ferroptosis.
🧬 Mechanism
⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — G6PD
No curated PDB or AlphaFold mapping for G6PD 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 G6PD, SLC7A11, GPX4.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
📊 Market Indicators
💾 Resource Usage
No resource usage or linked notebooks recorded for this hypothesis yet.
▸Metadataorigin_type: debate_synthesizer
| origin_type | debate_synthesizer |
| target_gene | G6PD, SLC7A11, GPX4 |
| _schema_version | 1 |
| composite_score | 0.55 |