The compound acts primarily through HSP70 and lysosomal proteostasis pathways, reducing seeded aggregate burden in intact neurons.
Curated pathway from expert analysis
flowchart TD
A["Ubiquitinated Cargo<br/>Misfolded Proteins/Organelles"]
B["SQSTM1/p62 UBA Domain<br/>Ubiquitin Chain Recognition"]
C["SQSTM1 Oligomerization<br/>LIR Motif Exposure"]
D["LC3-II Interaction<br/>Autophagosome Docking"]
E["Cargo Sequestration<br/>Autophagosome Engulfment"]
F["NRF2 Release<br/>KEAP1-p62 Competition"]
G["Lysosomal Degradation<br/>Proteostasis Restored"]
H["SQSTM1 Aggregates<br/>ALS/FTD Pathology"]
A --> B
B --> C
C --> D
D --> E
E --> G
B --> F
F -.->|"antioxidant"| G
C --> H
style A fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style G fill:#1b5e20,stroke:#81c784,color:#81c784
style H fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for SQSTM1 yet. Search RCSB →
Median TPM across 13 brain regions for SQSTM1 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 SQSTM1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF we apply rutin (10 µM) to iPSC‑derived cortical neurons in which SQSTM1 (p62) has been knocked out by CRISPR for 7 days, THEN the rutin‑induced reduction in tau aggregate burden observed in SQSTM1 | Loss of rutin‑mediated tau aggregate reduction (<10% change) in SQSTM1 knockout neurons, while wild‑type neurons show ≥30% reduction | — no observation — | pending | 0.55 |
| IF we treat primary cortical neurons seeded with human P301S tau fibrils with rutin (10 µM) once daily for 7 days, THEN we will observe a statistically significant reduction of at least 30% in deterge | ≥30% decrease in detergent‑insoluble tau as quantified by Western blot or ELISA | — no observation — | pending | 0.65 |