🧪
hypothesis

Labile iron pool expansion amplifies genotype-specific ALS ferroptosis

Hypothesis

Labile iron pool expansion amplifies genotype-specific ALS ferroptosis

SOD1, TDP-43, and FUS pathology may converge on impaired iron buffering in motor neurons and glia, increasing labile iron that catalyzes lipid peroxide propagation.
🧬 FTL🩺 neurodegeneration🎯 Composite 66%💱 $0.58▼20.2%proposed
EvidenceModerate (58%)📖 0 cit🗣 1 debates 3 support 2 oppose
✓ All Quality Gates Passed
Mechanistic 0.68 (15%) Evidence 0.64 (15%) Novelty 0.55 (12%) Feasibility 0.69 (12%) Impact 0.72 (12%) Druggability 0.70 (10%) Safety 0.52 (8%) Competition 0.55 (6%) Data Avail. 0.65 (5%) Reproducible 0.62 (5%) KG Connect 0.58 (8%) 0.664 composite
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Composite66%

🧪 Overview

SOD1, TDP-43, and FUS pathology may converge on impaired iron buffering in motor neurons and glia, increasing labile iron that catalyzes lipid peroxide propagation. Biomarker-guided iron buffering should benefit only the subgroup with demonstrable iron and lipid-peroxidation elevation.

🧬 Mechanism

🧬 Curated Mechanism Pathway

Curated pathway from expert analysis

flowchart TD
A["SOD1 pathology"]
B["TDP-43 pathology"]
C["FUS pathology"]
D["FTL dysfunction"]
E["Impaired iron buffering in motor neurons and glia"]
F["Labile iron pool expansion"]
G["Catalysis of lipid peroxide propagation"]
H["Lipid peroxidation accumulation"]
I["Ferroptosis"]
J["Motor neuron death"]
K["Biomarker-guided patient stratification"]
L["Identification of iron-elevated subgroup"]
M["Iron chelation therapy"]
N["Reduced labile iron"]
O["Neuroprotection"]
A -->|"converges"| D
B -->|"converges"| D
C -->|"converges"| D
D -->|"causes"| E
E -->|"enables"| F
F -->|"drives"| G
G -->|"propagates"| H
H -->|"induces"| I
I -->|"results in"| J
K -->|"identifies"| L
L -->|"enables targeted"| M
M -->|"reduces"| N
N -->|"prevents"| G
M -->|"provides"| O
J -->|"disease progression"| P["ALS phenotype"]
P -->|"clinical outcome"| Q["Neurological deficit"]
style A fill:#ef5350,color:#0d0d1a
style B fill:#ef5350,color:#0d0d1a
style C fill:#ef5350,color:#0d0d1a
style D fill:#ef5350,color:#0d0d1a
style E fill:#ef5350,color:#0d0d1a
style F fill:#ef5350,color:#0d0d1a
style G fill:#4fc3f7,color:#0d0d1a
style H fill:#ef5350,color:#0d0d1a
style I fill:#ef5350,color:#0d0d1a
style J fill:#ef5350,color:#0d0d1a
style K fill:#81c784,color:#0d0d1a
style L fill:#81c784,color:#0d0d1a
style M fill:#81c784,color:#0d0d1a
style N fill:#81c784,color:#0d0d1a
style O fill:#ffd54f,color:#0d0d1a

⚖️ Evidence

⚖️ Evidence Matrix2 supports1 contradicts
Supports
Inhibition of keratinocyte ferroptosis suppresses psoriatic inflammation.
Cell Death Dis2021PMID:34707088
Supports
Neuroferritinopathy.
1993PMID:20301320
Contradicts
Neurodegeneration with Brain Iron Accumulation Disorders Overview.
1993PMID:23447832
📖 Linked Papers

No linked papers recorded for this hypothesis yet.

🏥 Translation

🧬 3D Protein Structure — FTL

No curated PDB or AlphaFold mapping for FTL yet. Search RCSB →

🧠 GTEx v10 Brain ExpressionJSON

Median TPM across 13 brain regions for FTL from GTEx v10.

Spinal cord cervical c-16687 Substantia nigra3746 Amygdala3455 Nucleus accumbens basal ganglia3051 Caudate basal ganglia3027 Putamen basal ganglia2911 Anterior cingulate cortex BA242639 Hippocampus2630 Frontal Cortex BA92409 Hypothalamus2387 Cortex2230 Cerebellum1139 Cerebellar Hemisphere1100median TPM (GTEx v10)

💉 Clinical Trials (1)Relevance: 72%

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Untitled TrialUnknown
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No curated ClinVar variants loaded for this hypothesis.

Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.

🔍 Search ClinVar for FTL →

No DepMap CRISPR Chronos data found for FTL.

Run python3 scripts/backfill_hypothesis_depmap.py to populate.

🏆 Tournament

🏆 Arenas / Elo

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📊 Market Indicators

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Events (7d)
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💾 Resource Usage

No resource usage or linked notebooks recorded for this hypothesis yet.

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