Covalent modulation of transporters or metabolic enzymes changes local receptor occupancy in a context-dependent manner.
Curated pathway from expert analysis
flowchart TD
A["Adenosine Accumulation<br/>Metabolic Stress or Hypoxia"]
B["ADORA2A Engagement<br/>Gi-coupled Anti-inflammatory Receptor"]
C["cAMP Suppression<br/>PKA Activity Reduction"]
D["Microglial Activation Threshold Raised<br/>Pro-inflammatory Mediator Release Reduced"]
E["Neuroprotection<br/>Reduced Glutamate Toxicity and Oxidative Stress"]
F["ADORA2A Blockade<br/>Pro-inflammatory Activation Restored"]
A --> B
B --> C
C --> D
D --> E
F -.->|"counteracts"| B
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style E fill:#1b5e20,stroke:#81c784,color:#81c784
style F 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 human SH-SY5Y neuroblastoma cells are treated with parthenolide (10 μM, 2-hour incubation), THEN extracellular adenosine concentration will increase by >50% compared to vehicle-treated controls, as | Extracellular adenosine will increase from baseline ~200 nM to >300 nM in parthenolide-treated cultures | — no observation — | pending | 0.65 |
| IF rat primary cortical neurons are pretreated with NBTI (10 μM, equilibrated nucleoside transporter inhibitor) followed by parthenolide (10 μM, 2 hours), THEN the parthenolide-induced increase in ext | Adenosine concentration in parthenolide+NBTI condition will not differ significantly from NBTI-only control (within 20% of baseline) | — no observation — | pending | 0.55 |