The same signal may be beneficial early and damaging late. Testing microglial inflammasome tone with dietary fiber challenge should reveal a disease-stage interaction and define when intervention is protective versus counterproductive.
Curated pathway from expert analysis
flowchart TD
A["Amyloid-beta/Tau<br/>Priming Signal"]
B["Lysosomal Damage<br/>Cathepsin B Release"]
C["NLRP3 Sensor<br/>NEK7 Binding"]
D["ASC Speck Formation<br/>PYD Domain Oligomerization"]
E["Pro-Caspase-1<br/>CARD Domain Recruitment"]
F["Active Caspase-1<br/>Cleavage Activation"]
G["IL-1B/IL-18 Secretion<br/>Pro-inflammatory"]
H["Pyroptosis<br/>Gasdermin D Pore"]
I["Feed-Forward Loop<br/>Sustained SASP Inflammasome"]
A --> C
B --> C
C --> D
D --> E
E --> F
F --> G
F --> H
G --> I
I -.->|"amplifies"| C
style A fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style H fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style I fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo curated PDB or AlphaFold mapping for MICROGLIAL 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 microglial inflammasome tone.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
No resource usage or linked notebooks recorded for this hypothesis yet.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF inflammasome tone is the actionable state, THEN dysbiosis-induced cognitive impairment will track caspase-1-positive microglia with r >=0.35 across animals within 10 weeks. | Caspase-1-positive microglial fraction correlates with memory deficit severity at r >=0.35. | — no observation — | pending | 0.57 |
| IF microglial inflammasome tone defines the treatment window, THEN NLRP3 inhibition during early dysbiosis will reduce brain IL-1B by >=40%, but the same treatment after established neuronal injury wi | Early-treatment arm shows >=40% IL-1B reduction and late-treatment arm shows <15% reduction relative to matched controls. | — no observation — | pending | 0.59 |