Endosomal escape determines whether transferred tau becomes pathogenic
🧪 Overview
Some tau species are transferred between neurons but remain non-pathogenic because they stay trapped in degradative endosomal routes. Seed-competent tau either escapes into cytosol or traffics through compartments that expose it to soluble tau substrate.
🧬 Mechanism
Curated pathway from expert analysis
flowchart TD
A["RAB7A"] --> B["Late endosome maturation"]
A --> C["Endosomal trafficking regulation"]
B --> D["Lysosomal fusion and delivery"]
C --> E{"Endosomal membrane integrity"}
E --> F["Endosomal escape"]
E --> G["Endosomal retention"]
F --> H["Cytosolic tau exposure"]
G --> I["Delivery to lysosome"]
I --> J["Lysosomal degradation"]
J --> K["Non-pathogenic tau clearance"]
H --> L["Seed-competent tau formation"]
L --> M["Tau aggregation and propagation"]
M --> N["Neuronal dysfunction"]
style A fill:#4fc3f7,color:#0d0d1a
style B fill:#4fc3f7,color:#0d0d1a
style C fill:#4fc3f7,color:#0d0d1a
style D fill:#4fc3f7,color:#0d0d1a
style I fill:#4fc3f7,color:#0d0d1a
style J fill:#4fc3f7,color:#0d0d1a
style E fill:#ffd54f,color:#0d0d1a
style F fill:#ef5350,color:#0d0d1a
style G fill:#81c784,color:#0d0d1a
style H fill:#ef5350,color:#0d0d1a
style K fill:#81c784,color:#0d0d1a
style L fill:#ef5350,color:#0d0d1a
style M fill:#ef5350,color:#0d0d1a
style N fill:#ef5350,color:#0d0d1a⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — RAB7A
No curated PDB or AlphaFold mapping for RAB7A yet. Search RCSB →
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for RAB7A from GTEx v10.
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 RAB7A.
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.
▸Metadatasource: v1_phase_c_backfill · origin_type: gap_debate
| source | v1_phase_c_backfill |
| origin_type | gap_debate |
| _schema_version | 1 |