Combine subthreshold RGS6 rescue with D2-pathway modulation to test whether benefit requires convergent normalization of autoreceptor-Gi/o signaling. This remains secondary to monotherapy studies and should not be prioritized until RGS6-alone efficacy and the relevant signaling mechanism are established.
Curated pathway from expert analysis
flowchart TD
A["RGS6 Restoration<br/>Regulator of G Protein Signaling 6"]
B["D2 Autoreceptor<br/>Pathway Modulation"]
C["G Protein Signaling<br/>Normalized"]
D["Dopamine Neurotransmission<br/>Homeostasis Restored"]
E["Combined RGS6 + D2<br/>Therapeutic Approach"]
F["RGS6 as Central<br/>Modulation Target"]
A --> B
B --> C
C --> D
D --> E
E --> F
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style F fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for RGS6 yet. Search RCSB →
Median TPM across 13 brain regions for RGS6 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 RGS6.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF subthreshold RGS6 restoration via AAV9‑RGS6 in adult rats is combined with a low‑dose D2 antagonist (eticlopride), THEN we will see a synergistic reduction in dopaminergic neuron loss in the substa | Stereological counts of TH‑positive neurons in the SNpc will be at least 40 % higher in the combination group compared with the AAV‑RGS6 alone group and at leas | — no observation — | pending | 0.50 |
| IF subthreshold AAV-mediated RGS6 overexpression combined with chronic low-dose D2 agonist (quinpirole) is administered to MPTP‑lesioned C57BL/6 mice, THEN we will observe a significantly greater impr | Rotarod latency in the combination group will be at least 30 % longer than in the vehicle group, exceeding the improvement seen with either AAV‑RGS6 or quinpiro | — no observation — | pending | 0.55 |