P2X7 Receptor Antagonism to Block ATP-Induced Microglial Pyroptosis
Curated pathway from expert analysis
flowchart TD
A["Extracellular<br/>ATP"]
B["P2X7 Receptor<br/>Activation"]
C["PANX1 Pannexin<br/>Channel Opening"]
D["NLRP3<br/>Inflammasome"]
E["Caspase-1<br/>Activation"]
F["Gasdermin D<br/>Pyroptosis"]
G["IL-1beta / IL-18<br/>Release"]
H["Microglial<br/>Pyroptosis"]
A --> B
B --> C
C --> D
D --> E
E --> F
F --> G
F --> H
style A fill:#004d40,stroke:#80cbc4,color:#80cbc4
style B fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style H fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
Median TPM across 13 brain regions for P2RX7 (P2X7 receptor) → PANX1 → NLRP3 → Caspase-1/Gasdermin D 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 P2RX7 (P2X7 receptor) → PANX1 → NLRP3 → Caspase-1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF C57BL/6 mice receive intraperitoneal P2X7 antagonist (BBG, 50 mg/kg) 1 hour before LPS (5 mg/kg) injection THEN microglial NLRP3 inflammasome activation and serum IL-1β levels will decrease by >40% | Iba1+ microglia will show reduced NLRP3 immunofluorescence intensity and caspase-1 activity; serum IL-1β will drop from ~800 pg/mL to <480 pg/mL | — no observation — | pending | 0.65 |
| IF BV2 microglial cells are pretreated with 10 μM A438079 (P2X7 receptor antagonist) THEN ATP (5 mM)-induced pyroptosis will be reduced by >50% as measured by lactate dehydrogenase release, compared t | LDH release will decrease from ~80% (ATP alone) to <40% (ATP + antagonist), with concomitant reduction in Gasdermin D cleavage and cleaved caspase-1 levels | — no observation — | pending | 0.75 |