🧪
hypothesis

Pentose Phosphate Pathway Suppression Enables Ferroptosis Vulnerability

Hypothesis

Pentose Phosphate Pathway Suppression Enables Ferroptosis Vulnerability

NADPH depletion from PPP inhibition creates ferroptosis susceptibility in vulnerable neurons.
🧬 G6PD, SLC7A11, GPX4🩺 neurodegeneration🎯 Composite 55%💱 $0.54▼2.4%proposed
EvidencePending (0%)📖 0 cit🗣 1 debates 3 support 3 oppose
✓ All Quality Gates Passed
Mechanistic 0.58 (15%) Evidence 0.65 (15%) Novelty 0.72 (12%) Feasibility 0.45 (12%) Impact 0.55 (12%) Druggability 0.40 (10%) Safety 0.35 (8%) Competition 0.60 (6%) Data Avail. 0.65 (5%) Reproducible 0.55 (5%) KG Connect 0.50 (8%) 0.550 composite
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Composite55%

🧪 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

No curated mechanism pathway recorded for this hypothesis.

⚖️ Evidence

⚖️ Evidence Matrix3 supports3 contradicts
Supports
G6PD activity is decreased in AD brain
PMID:31666140
Supports
System Xc- inhibition triggers ferroptosis in neuronal cultures
PMID:30319128
Supports
Ferroptosis markers elevated in AD and ALS patient tissue
PMID:30898851
Contradicts
G6PD activity decrease was only 15-20% in AD cortex, within normal aging variance
PMID:31666140
Contradicts
GPX4 overexpression fails to prevent disease in some ALS models
PMID:29872153
Contradicts
Brain tissue has high ascorbate levels that can reduce lipid peroxides independently of GPX4
PMID:31666140
📖 Linked Papers

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.

🔍 Search ClinVar for G6PD, SLC7A11, GPX4 →

No DepMap CRISPR Chronos data found for G6PD, SLC7A11, GPX4.

Run python3 scripts/backfill_hypothesis_depmap.py to populate.

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💾 Resource Usage

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