Use dopaminergic-neuron-selective expression of RGS6 to distinguish true cell-autonomous rescue from broader circuit or glial effects. This is best treated as a mechanistic refinement of RGS6 rescue rather than a separate therapeutic platform, and should only advance if generic SNpc re-expression shows efficacy.
Curated pathway from expert analysis
flowchart TD
A["TH-neuron-selective<br/>RGS6 Expression"]
B["Cell-autonomous<br/>Therapeutic Rescue"]
C["Circuit / Glial<br/>Effect Exclusion"]
D["Dopaminergic<br/>Neuron Protection"]
A --> B
B --> C
B --> D
style A fill:#6a1b9a,stroke:#ce93d8,color:#ce93d8
style D 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 we compare behavioral recovery (rotarod latency and spontaneous locomotion) between MPTP mice receiving TH-neuron-restricted RGS6 rescue versus mice receiving equivalent AAV-mediated RGS6 expressio | Motor behavior will normalize in the TH-RGS6 group (≥50% recovery) but not in the GFAP-RGS6 group, confirming cell-autonomous specificity. | — no observation — | pending | 0.45 |
| IF we selectively overexpress RGS6 exclusively in TH+ dopaminergic neurons via stereotactic AAV9-DIO-RGS6 injection in MPTP-lesioned mice (with Cre expressed only in TH+ cells), THEN stereological cou | TH+ neuron survival in SNpc will be significantly greater in the TH-RGS6 group (mean ≥ 40% increase vs. control), with corresponding reduction in terminal loss | — no observation — | pending | 0.55 |