ID: h-28c25ed899
Hypothesis

OPC Maturation Block via PDGFRA/LXRβ

OPCs show failure to differentiate due to elevated PDGFRA oscillation and hypomethylation of maturation genes.
🧬 PDGFRA🩺 neurodegeneration🎯 Composite 62%💱 $0.56▼10.2%proposed
EvidencePending (0%)📖 0 cit🗣 1 debates 3 support 2 oppose
✓ All Quality Gates Passed
Mechanistic 0.65 (15%) Evidence 0.60 (15%) Novelty 0.65 (12%) Feasibility 0.68 (12%) Impact 0.68 (12%) Druggability 0.72 (10%) Safety 0.58 (8%) Competition 0.65 (6%) Data Avail. 0.55 (5%) Reproducible 0.60 (5%) KG Connect 0.50 (8%) 0.620 composite

🧪 Overview

OPCs show failure to differentiate due to elevated PDGFRA oscillation and hypomethylation of maturation genes. OPCs in AD brains show sustained PDGFRA expression, reduced MBP and PLP1, and epigenetic silencing of myelin genes, reflecting maturation arrest contributing to demyelination independent of primary oligodendrocyte loss.

🧬 Mechanism

🔗 Mechanism from KG for PDGFRA

Auto-built from this analysis's top knowledge-graph edges.

graph TD
    PDGFRA["PDGFRA"] -->|causes| OPC_maturation_arrest["OPC maturation arrest"]
    PDGFRA_1["PDGFRA"] -.->|inhibits| OPC_differentiation["OPC differentiation"]
    PDGFRA_oscillation["PDGFRA oscillation"] -->|causes| OPC_maturation_arrest_2["OPC maturation arrest"]
    style PDGFRA fill:#ce93d8,stroke:#333,color:#000
    style OPC_maturation_arrest fill:#4fc3f7,stroke:#333,color:#000
    style PDGFRA_1 fill:#ce93d8,stroke:#333,color:#000
    style OPC_differentiation fill:#4fc3f7,stroke:#333,color:#000
    style PDGFRA_oscillation fill:#4fc3f7,stroke:#333,color:#000
    style OPC_maturation_arrest_2 fill:#4fc3f7,stroke:#333,color:#000

⚖️ Evidence

⚖️ Evidence Matrix3 supports2 contradicts
Supports
OPC dysregulation documented in AD
Supports
OPC maturation mechanisms studied in multiple sclerosis
Supports
Demyelination observed in AD brains
Contradicts
PDGFRA oscillation is normal OPC proliferation feature
Contradicts
OPCs in aged brain already maturation-arrested independent of neurodegeneration
📖 Linked Papers

No linked papers recorded for this hypothesis yet.

🏥 Translation

🧬 3D Protein Structure — PDGFRA

No curated PDB or AlphaFold mapping for PDGFRA 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 PDGFRA →

No DepMap CRISPR Chronos data found for PDGFRA.

Run python3 scripts/backfill_hypothesis_depmap.py to populate.

🏆 Tournament

🏆 Arenas / Elo

No arena matches recorded yet. Browse Arenas →

📊 Market Indicators

7d Trend
Stable
7d Momentum
▼ 0.7%
Volatility
Low
0.0018
Events (7d)
3
Price History
▼10.2%

💾 Resource Usage

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

Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesizer
sourcev1_phase_c_backfill
origin_typedebate_synthesizer
_schema_version1
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting 0 contradicting 0 neutral
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