ID: h-0ca9a295f6
Hypothesis
Rutin enhances chaperone and autophagic clearance of misfolded tau
The compound acts primarily through HSP70 and lysosomal proteostasis pathways, reducing seeded aggregate burden in intact neurons.
EvidencePending (0%)📖 4 cit🗣 1 debates✓ 4 support✗ 1 oppose
✓ All Quality Gates Passed
🧪 Overview
The compound acts primarily through HSP70 and lysosomal proteostasis pathways, reducing seeded aggregate burden in intact neurons.
🧬 Mechanism
🧬 Curated Mechanism Pathway
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:#ef9a9a⚖️ Evidence
⚖️ Evidence Matrix4 supports1 contradicts
Supports
Targeting inflammation, autophagy, and apoptosis by troxerutin attenuates neurodegeneration.
Supports
p62 filaments capture and present ubiquitinated cargos for autophagy.
Supports
The upstream pathway of mTOR-mediated autophagy in liver diseases.
Supports
Autophagy regulation by polyphenolic compounds as a therapeutic strategy.
Contradicts
Without pathway-ablation data this model is too nonspecific to prioritize first.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — SQSTM1
No curated PDB or AlphaFold mapping for SQSTM1 yet. Search RCSB →
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for SQSTM1 from GTEx v10.
💉 Clinical Trials
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.
💰 Estimated Development
Cost
$0
Timeline
—
🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
7d Trend
↔
Stable
7d Momentum
▼ 0.6%
Volatility
Low
0.0021
Events (7d)
3
Price History
▼8.5%💾 Resource Usage
LLM Tokens
1,743
$0.0052
Total Cost
$0.0052
🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| 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 |
🔮 Falsifiable Predictions (2)
pendingconf 65%
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 detergent‑insoluble tau levels compared to vehicle‑treated neurons within 2 weeks after treatment initiatio
Predicted outcome: ≥30% decrease in detergent‑insoluble tau as quantified by Western blot or ELISA
Falsification: No statistically significant change in detergent‑insoluble tau (i.e., <10% change) after rutin treatment, indicating the compound does not reduce seeded tau aggregates under these conditions
pendingconf 55%
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 wild‑type neurons will be abolished (i.e., <10% change), indicating SQSTM1 is required for rutin’s e
Predicted outcome: Loss of rutin‑mediated tau aggregate reduction (<10% change) in SQSTM1 knockout neurons, while wild‑type neurons show ≥30% reduction
Falsification: Rutin still reduces tau aggregates by ≥30% in SQSTM1 knockout neurons, disproving the requirement of SQSTM1 for rutin’s action
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesizer
| source | v1_phase_c_backfill |
| origin_type | debate_synthesizer |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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