Compounds that extend HSP70's ATPase cycle specifically when bound to tau substrates, trapping tau in non-productive chaperone complexes and leading to tau sequestration and degradation through quality control pathways.
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 HSPA1A ATPase inhibition (15 μM PES) is applied to iPSC-derived cortical neurons from a PSP patient cohort for 48 hours, THEN total tau protein will be reduced by >50% relative to vehicle controls, | >50% reduction in total tau (normalized to βIII-tubulin loading control) in treatment vs. control; reversal of effect with bortezomib co-treatment. | — no observation — | pending | 0.58 |
| IF HSPA1A ATPase activity is selectively inhibited (e.g., 2-phenylethynesulfonamide at 20 μM) in human neuroglioma cells overexpressing 2N4R tau for 24 hours, THEN tau-HSPA1A complex abundance will in | Increased tau-HSPA1A complex formation (+>100%) and reduced soluble tau concentration (-40%), both quantified by co-immunoprecipitation and quantitative western | — no observation — | pending | 0.62 |