Inhibitors containing molecular recognition elements that only bind HSP70 when it adopts conformations specific to pathological tau engagement, exploiting differences in HSP70 structure when bound to misfolded versus properly folded tau species.
Auto-built from this analysis's top knowledge-graph edges.
graph TD
HSPA1A["HSPA1A"] -->|protein interactio| STUB1["STUB1"]
MAPT["MAPT"] -->|regulates| HSPA1A_1["HSPA1A"]
Bifunctional_PROTACs["Bifunctional PROTACs"] -->|targets| HSPA1A_2["HSPA1A"]
HSPA1A_3["HSPA1A"] -->|regulates| tau_protein["tau protein"]
HSPA1A_4["HSPA1A"] -->|regulates| proteasomal_degradation_p["proteasomal degradation pathway"]
style HSPA1A fill:#ce93d8,stroke:#333,color:#000
style STUB1 fill:#ce93d8,stroke:#333,color:#000
style MAPT fill:#ce93d8,stroke:#333,color:#000
style HSPA1A_1 fill:#ce93d8,stroke:#333,color:#000
style Bifunctional_PROTACs fill:#4fc3f7,stroke:#333,color:#000
style HSPA1A_2 fill:#4fc3f7,stroke:#333,color:#000
style HSPA1A_3 fill:#4fc3f7,stroke:#333,color:#000
style tau_protein fill:#4fc3f7,stroke:#333,color:#000
style HSPA1A_4 fill:#4fc3f7,stroke:#333,color:#000
style proteasomal_degradation_p fill:#81c784,stroke:#333,color:#000No linked papers recorded for this hypothesis yet.
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 HSPA1A.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF we compare the binding affinity (Kd) of the conformation-selective inhibitor for HSP70 immunoprecipitated from tau-filament-enriched AD brain homogenates vs. age-matched healthy hippocampus, THEN w | ≥5-fold selectivity for disease-state HSP70 (Kd ratio disease/normal ≥5) | — no observation — | pending | 0.00 |
| IF we administer a conformation-selective HSP70 inhibitor (vs. vehicle) to rTg4510 tauopathy mice for 8 weeks at 10mg/kg/day, THEN we will observe at least a 30% reduction in Sarkisovan-insoluble tau | ≥30% decrease in Sarkisovan-insoluble tau in hippocampus; increased soluble tau ratio; reduced tau seeding in bioassay | — no observation — | pending | 0.00 |