Heat-shock signaling either directly or indirectly reduces tau expression as chaperone programs dominate the stress response.
Curated pathway from expert analysis
flowchart TD
A["HSF1 Activation<br/>Heat-Shock Transcription Program"]
B["HSP70/HSP90 Chaperone Induction<br/>Proteome Refolding Capacity"]
C["Tau Folding Pressure Reduced<br/>Misprocessing Contained"]
D["Aggregate Clearance Bias<br/>Proteostasis Dominates Stress Response"]
E["Tau Burden Falls<br/>Neuronal Survival Improves"]
A --> B
B --> C
B --> D
C --> E
D --> E
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style E fill:#1b5e20,stroke:#81c784,color:#81c784No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for HSF1 yet. Search RCSB →
Median TPM across 13 brain regions for HSF1 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 HSF1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF HSF1 is genetically activated via AAV9-mediated CRISPR-dCas9-HSF1 overexpression in the hippocampus of 3xTG-AD mice at 6 months of age, THEN both total tau (Tau5) and phosphorylated tau (AT8) will | ≥40% reduction in hippocampal total tau and phosphorylated tau (AT8) with ≥25% increase in 20S proteasome activity, alongside ≥3-fold elevation of HSPA1A (HSP70 | — no observation — | pending | 0.55 |
| IF HSF1 is pharmacologically activated in N2a neuroblastoma cells or human iPSC-derived neurons with HSF1A (10 μM, 6 hours), THEN MAPT (tau) protein levels will decrease by ≥30% compared to vehicle co | ≥30% reduction in total tau protein (MAPT) with concurrent ≥2-fold increase in HSP70 (HSPA1A) as positive control for HSF1 activation. | — no observation — | pending | 0.65 |