This hypothesis proposes that HBOT reduces ROS-mediated NF-κB activation and NLRP3 inflammasome assembly, promoting anti-inflammatory M2 polarization that enhances amyloid phagocytosis. It benefits from clinical relevance (neuroinflammation is a consistent AD finding) but relies on an oversimplified M1/M2 binary framework that does not capture disease-associated microglia (DAM) complexity.
Curated pathway from expert analysis
flowchart TD
A["Target Gene: NLRP3"]
B["Molecular Mechanism<br/>Pathway Activation"]
C["Cellular Phenotype<br/>Neuronal / Glial Response"]
D["Network Effect<br/>Circuit-Level Consequence"]
E["Disease Relevance<br/>Neurodegeneration Link"]
A --> B --> C --> D --> E
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style E fill:#1b5e20,stroke:#81c784,color:#81c784No linked papers recorded for this hypothesis yet.
Median TPM across 13 brain regions for NLRP3 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 NLRP3.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF APP/PS1ΔE9 transgenic mice receive intermittent HBOT (2.0 ATA, 100% O2, 60 min/session, 3 sessions/week for 8 weeks) THEN hippocampal NLRP3 inflammasome activity (measured by caspase-1 FLICA assay | NLRP3 inflammasome activity will be suppressed by ≥30% in HBOT-treated mice relative to sham controls, with corresponding reduction in downstream inflammatory c | — no observation — | pending | 0.65 |
| IF 5xFAD mice receive intermittent HBOT (2.0 ATA, 100% O2, 60 min/session, 3 sessions/week for 8 weeks) THEN the ratio of M2 (CD206+/Arg1+) to M1 (iNOS+/CD16/32+) microglia in cortical and hippocampal | M2/M1 microglial polarization ratio will increase by ≥25% in HBOT-treated mice, indicating a shift toward neuroprotective phenotype with enhanced amyloid phagoc | — no observation — | pending | 0.60 |