ID: h-86d0aa1ede
Hypothesis

Rutin reduces ROS- and metal-driven tau oligomer nucleation

Chelation of redox-active metals and suppression of oxidative cross-linking reduce formation of toxic tau oligomers rather than binding mature fibrils directly.
🧬 MAPT🩺 neurodegeneration🎯 Composite 60%💱 $0.55▼8.3%proposed
EvidencePending (0%)📖 1 cit🗣 1 debates 6 support 1 oppose
✓ All Quality Gates Passed
Mechanistic 0.64 (15%) Evidence 0.51 (15%) Novelty 0.61 (12%) Feasibility 0.75 (12%) Impact 0.57 (12%) Druggability 0.48 (10%) Safety 0.71 (8%) Competition 0.52 (6%) Data Avail. 0.62 (5%) Reproducible 0.61 (5%) KG Connect 0.24 (8%) 0.602 composite

🧪 Overview

Chelation of redox-active metals and suppression of oxidative cross-linking reduce formation of toxic tau oligomers rather than binding mature fibrils directly.

🧬 Mechanism

🧬 Curated Mechanism Pathway

Curated pathway from expert analysis

flowchart TD
    A["Target Gene: MAPT"]
    B["Molecular Mechanism<br/>Pathway Activation"]
    C["Cellular Phenotype<br/>Neuronal / Glial Response"]
    D["Network Effect<br/>Circuit-Level Consequence"]
    E["Disease Relevance<br/>Neurodegeneration Link"]
    A --> B --> C --> D --> E
    style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
    style E fill:#1b5e20,stroke:#81c784,color:#81c784

⚖️ Evidence

⚖️ Evidence Matrix6 supports1 contradicts
Supports
Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer's disease.
Brain Res2021PMID:34116706high
Supports
The Neuroprotective Potentiality of Flavonoids on Alzheimer's Disease.
Int J Mol Sci2022PMID:36499159
Supports
EGCG impedes human Tau aggregation and interacts with Tau.
Sci Rep2020PMID:32724104
Supports
Baicalein inhibits heparin-induced Tau aggregation by initializing non-toxic Tau oligomer formation.
Cell Commun Signal2021PMID:33579328
Supports
Phytomolecules as Alzheimer's therapeutics: A comprehensive review.
Eur J Med Chem2025PMID:39999743
Supports
Study on the neuroprotective effects of Genistein on Alzheimer's disease.
Brain Behav2021PMID:33704934
Contradicts
Generic antioxidant effects may not explain structural selectivity for pathogenic tau seeds.
📖 Linked Papers

No linked papers recorded for this hypothesis yet.

🏥 Translation

🧬 3D Protein Structure — MAPT

🧬 PDB 5O3L Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

🧠 GTEx v10 Brain ExpressionJSON

Median TPM across 13 brain regions for MAPT from GTEx v10.

Cerebellum209 Cerebellar Hemisphere199 Cortex152 Frontal Cortex BA9146 Anterior cingulate cortex BA24101 Hypothalamus86.4 Amygdala73.5 Nucleus accumbens basal ganglia72.2 Hippocampus72.1 Caudate basal ganglia64.7 Putamen basal ganglia58.1 Substantia nigra56.8 Spinal cord cervical c-149.2median TPM (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.

🔍 Search ClinVar for MAPT →

No DepMap CRISPR Chronos data found for MAPT.

Run python3 scripts/backfill_hypothesis_depmap.py to populate.

💰 Estimated Development
Cost
$0
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📊 Market Indicators

7d Trend
Stable
7d Momentum
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Volatility
Low
0.0027
Events (7d)
3
Price History
▼8.3%

💾 Resource Usage

LLM Tokens
1,743
$0.0052
Total Cost
$0.0052

🔮 Predictions

🔎 Predictions vs Observations2 predictions · 0 with recorded observations
PredictionPredictedObservedStatusConf
IF recombinant human 2N4R tau monomers (10 μM) are incubated with CuCl₂ (25 μM) plus H₂O₂ (100 μM) in the presence of rutin (100 μM), THEN the concentration of tau oligomers (measured by oligomer-spec≥50% reduction in tau oligomer concentration with no change in fibril elongation rate— no observation —pending0.72
IF HEK293T cells transiently expressing 3×FLAG-hTau40 are pre-treated with rutin (30 μM) for 1 hour before exposure to 50 μM H₂O₂ for 2 hours, THEN intracellular tau oligomers (measured by amplified l≥40% reduction in oxidatively-induced tau oligomers with preserved total tau expression— no observation —pending0.68
🔮 Falsifiable Predictions (2)
pendingconf 72%
IF recombinant human 2N4R tau monomers (10 μM) are incubated with CuCl₂ (25 μM) plus H₂O₂ (100 μM) in the presence of rutin (100 μM), THEN the concentration of tau oligomers (measured by oligomer-specific sandwich ELISA using the TOC1 antibody) will decrease by ≥50% compared to vehicle control withi
Predicted outcome: ≥50% reduction in tau oligomer concentration with no change in fibril elongation rate
Falsification: No significant reduction in tau oligomer concentration (<20% change) or any decrease in ThT signal indicating fibril disruption, which would indicate rutin acts on mature fibrils rather than nucleatio
pendingconf 68%
IF HEK293T cells transiently expressing 3×FLAG-hTau40 are pre-treated with rutin (30 μM) for 1 hour before exposure to 50 μM H₂O₂ for 2 hours, THEN intracellular tau oligomers (measured by amplified luminescence proximity assay) will decrease by ≥40% compared to H₂O₂-only controls at 24 hours post-t
Predicted outcome: ≥40% reduction in oxidatively-induced tau oligomers with preserved total tau expression
Falsification: No reduction or increase in tau oligomer levels despite antioxidant treatment, or reduction in total tau suggesting cytotoxicity rather than specific nucleation inhibition
Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesizer
sourcev1_phase_c_backfill
origin_typedebate_synthesizer
_schema_version1
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting 0 contradicting 0 neutral
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