NF-kB suppression in glia decreases ectonucleotidase and cytokine programs that sustain extracellular adenosine, indirectly reducing ADORA2A pathway output in mood circuits.
Curated pathway from expert analysis
flowchart TD
A["ADORA2A<br/>Hypothesis Target"]
B["Pathway Dysregulation<br/>Cited Mechanism"]
C["Cellular Response<br/>Stress or Clearance Change"]
D["Neural Circuit Effect<br/>Synapse/Glia Vulnerability"]
E["AD<br/>Disease-Relevant Outcome"]
A --> B
B --> C
C --> D
D --> E
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style B fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style E fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
Median TPM across 13 brain regions for ADORA2A 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 ADORA2A.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF parthenolide reduces extracellular adenosine tone via glial NF-κB inhibition, THEN parthenolide treatment (2 mg/kg/day, 14 days) will decrease ADORA2A-mediated cAMP accumulation in mPFC synaptoneur | At least 50% reduction in forskolin-stimulated cAMP accumulation in mPFC synaptoneurosomes from parthenolide-treated CMS mice versus vehicle-treated CMS mice, w | — no observation — | pending | 0.68 |
| IF parthenolide is administered daily at 2 mg/kg (i.p.) for 14 days to male C57BL/6J mice undergoing chronic mild stress (CMS), THEN extracellular adenosine concentrations in medial prefrontal cortex | At least 40% reduction in extracellular adenosine (μM) in mPFC of parthenolide-treated CMS mice relative to vehicle-treated CMS mice, with no significant change | — no observation — | pending | 0.72 |