GABAergic Hub Stabilization Through α5-Subunit Inverse Agonists
Curated pathway from expert analysis
flowchart TD
A["GABAergic Hub Stabilization<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["Neurodegeneration<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.
No curated PDB or AlphaFold mapping for GABAERGIC yet. Search RCSB →
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 GABAergic Hub Stabilization.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF we administer a selective GABA-A α5-subunit inverse agonist (e.g., MRK-016 at 10 mg/kg, i.p.) to adult C57BL/6J mice for 14 consecutive days, THEN we will observe significant stabilization of GABAe | ≥30% reduction in firing variability (CV-ISI) of GABAergic hub neurons in α5 inverse agonist-treated mice relative to vehicle-treated controls after 14 days of | — no observation — | pending | 0.65 |
| IF we perform chemogenetic inhibition (hM4Di) of GABAergic hub neurons specifically in the anterior cingulate cortex while concurrently administering an α5-subunit inverse agonist (RG1662, 20 mg/kg/da | Partial restoration (≥40%) of ACC-centered functional connectivity metrics to non-stressed baseline levels within 3 weeks of combined intervention, as assessed | — no observation — | pending | 0.55 |