DNA damage and SASP signaling keep initiation suppressed, producing a durable upstream autophagy defect.
Curated pathway from expert analysis
flowchart TD
A["Growth Factor Signaling<br/>PI3K or AKT Pathway"]
B["mTORC1 Activation<br/>Rheb GTPase Mediated"]
C["S6K1 or 4EBP1 Phosphorylation<br/>Protein Synthesis Upregulation"]
D["Autophagy Inhibition<br/>ULK1 or ATG13 Suppression"]
E["Cap-Dependent Translation<br/>Synaptic Plasticity Proteins"]
F["mTORC2 or AKT Ser473<br/>Cell Survival and Metabolism"]
G["mTOR Inhibitor<br/>Rapamycin or Torin1"]
A --> B
B --> C
B --> D
C --> E
E --> F
G -.->|"inhibits"| B
style A fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style G fill:#1b5e20,stroke:#81c784,color:#81c784No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for MTOR yet. Search RCSB →
Median TPM across 13 brain regions for MTOR from GTEx v10.
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.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF DNA damage signaling is attenuated using ATM inhibitor (KU-60019, 5 µM) in irradiated mouse brain pericytes THEN mTORC1 activity will decrease and autophagy initiation markers will normalize, withi | Reduced p-S6K1(T389) to <30% of irradiated control levels, restored p-ULK1(S317) to ≥70% of non-irradiated baseline, and increased autophagosome count (GFP-LC3 | — no observation — | pending | 0.55 |
| IF mTORC1 is pharmacologically inhibited (rapamycin, 100 nM) in irradiated human brain pericytes THEN autophagy initiation will be restored, as evidenced by increased LC3-II/LC3-I ratio and enhanced U | Increased LC3-II/LC3-I ratio (>2-fold) and elevated p-ULK1(S317) (>1.5-fold) in irradiated pericytes treated with rapamycin versus vehicle control | — no observation — | pending | 0.65 |