The scaffold alters receptor signaling efficacy without strong orthosteric affinity by modifying redox-sensitive lipid nanodomains.
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 lipid raft integrity is pharmacologically disrupted with methyl-β-cyclodextrin (MβCD, 5 mM for 30 min) prior to parthenolide treatment, THEN the parthenolide-induced change in ADORA2A coupling effi | MβCD pretreatment attenuates parthenolide's effect on ADORA2A coupling by >50% | — no observation — | pending | 0.28 |
| IF striatal neurons or striatum-derived cell lines are treated with parthenolide (1–10 μM for 30–60 min), THEN ADORA2A G-protein coupling efficiency will change by >25% compared to vehicle control as | Significant shift in ADORA2A coupling efficiency (>25% change in either direction) | — no observation — | pending | 0.35 |