HBOT increases mTORC1 inhibition, promoting TFEB nuclear translocation and enhancing autophagy flux to clear pathological proteins. However, autophagy markers are easily misinterpreted (increased LC3-II can mean blocked flux), and the direction of autophagy regulation by oxygen is context-dependent. Rigorous flux validation with insoluble Aβ/tau clearance endpoints is required.
Curated pathway from expert analysis
flowchart TD
A["mTORC1 Hyperactivation<br/>Nutrient/Growth Signals"]
B["TFEB Phosphorylation<br/>Ser211 by mTORC1"]
C["14-3-3 Sequestration<br/>Cytoplasmic Retention"]
D["Lysosomal Biogenesis<br/>Blocked"]
E["Autophagic Flux<br/>Impaired"]
F["Tau/Amyloid Aggregate<br/>Accumulation"]
G["TFEB Activation<br/>Rapamycin or MCOLN1"]
H["Nuclear TFEB<br/>CLEAR Gene Expression"]
G --> H
H -.->|"rescues"| D
A --> B
B --> C
C --> D
D --> E
E --> F
style A fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style G fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style H fill:#1b5e20,stroke:#81c784,color:#81c784No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for TFEB yet. Search RCSB →
Median TPM across 13 brain regions for TFEB (TFE2) 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 TFEB (TFE2).
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF APP/PS1 transgenic mice receive HBOT (2.0 ATA, 60 min per session, 5 sessions/week for 4 weeks), THEN cortical insoluble Aβ42 levels will decrease by ≥30% compared to sham-treated littermate contro | ≥30% reduction in cortical insoluble Aβ42; TFEB nuclear localization increase ≥1.8-fold in cortical neurons; LC3-II/p62 ratio increased ≥1.5-fold indicating enh | — no observation — | pending | 0.62 |
| IF SH-SY5Y neuroblastoma cells with doxycycline-inducible TFEB overexpression are subjected to HBOT (2.0 ATA, 60 min) in a hyperbaric chamber, THEN lysosomal protease activity (Cathepsin D) will incre | Cathepsin D activity ≥2-fold; BODIPY-casein cleavage rate ≥40% increase; TFEB nuclear/cytosol ratio ≥2.5-fold; p62 half-life decreased by ≥50% indicating active | — no observation — | pending | 0.58 |