Restore oxidative metabolism in APOE4 microglia through CNS-penetrant mTOR modulators that reactivate oxidative phosphorylation while maintaining inflammatory responsiveness
Curated pathway from expert analysis
flowchart TD
A["APOE4 Microglial Dysfunction<br/>TREM2 mTORC1 Axis Dysregulated"]
B["mTORC1 Hyperactivation<br/>TREM2-Akt-mTOR Pathway"]
C["Oxidative Phosphorylation Suppressed<br/>Glycolytic Shift in Microglia"]
D["Inflammatory Priming<br/>Pro-Inflammatory Gene Program"]
E["CNS-Penetrant mTOR Modulator<br/>Rapamycin Analog Torin-2"]
F["mTORC1 Partial Inhibition<br/>Metabolic Flexibility Restored"]
G["OXPHOS Re-Engaged<br/>Anti-Inflammatory Phenotype"]
H["Inflammatory Responsiveness Preserved<br/>Not Full Immunosuppression"]
I["APOE4 Microglial Rescue<br/>AD Neuroinflammation Reduced"]
A --> B
B --> C
C --> D
E --> F
F --> G
F --> H
G --> I
H --> I
style B fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style I fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for MTOR yet. Search RCSB →
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 MTOR.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.