ID: h-1e70cd6400
Hypothesis
Rutin stabilizes a non-nucleating tau conformer through direct MAPT repeat-domain binding
Rutin engages exposed tau aggregation motifs and lowers early oligomer nucleation, with strongest support expected from cell-free seeding and structural footprinting assays.
EvidencePending (0%)📖 6 cit🗣 1 debates✓ 6 support✗ 1 oppose
✓ All Quality Gates Passed
🧪 Overview
Rutin engages exposed tau aggregation motifs and lowers early oligomer nucleation, with strongest support expected from cell-free seeding and structural footprinting assays.
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD
A["MAPT/Tau Protein<br/>Microtubule Stabilizer"]
B["CDK5/GSK3B Activation<br/>Kinase Dysregulation"]
C["Tau Hyperphosphorylation<br/>Ser396/Thr231/Ser202"]
D["Tau Detachment<br/>Microtubule Destabilized"]
E["Tau Oligomers<br/>Paired Helical Filaments"]
F["Neurofibrillary Tangles<br/>Intraneuronal Inclusions"]
G["Axonal Transport Failure<br/>Synaptic Dysfunction"]
H["Neurodegeneration<br/>Tauopathy Spread"]
A --> B
B --> C
C --> D
D --> E
E --> F
D --> G
G --> H
F --> H
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style C fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style H fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a⚖️ Evidence
⚖️ Evidence Matrix6 supports1 contradicts
Supports
Direct tau anti-aggregation can be resolved with orthogonal biophysics and seeding assays.
Supports
MAPT mutations, tauopathy, and mechanisms of neurodegeneration.
Supports
Endolysosomal impairment by binding of amyloid beta or MAPT/Tau to V-ATPase and rescue via the HYAL-CD44 axis in Alzheimer disease.
Supports
Tau-targeting antisense oligonucleotide MAPT(Rx) in mild Alzheimer's disease: a phase 1b, randomized, placebo-controlled trial.
Supports
ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids.
Supports
The six brain-specific TAU isoforms and their role in Alzheimer's disease and related neurodegenerative dementia syndromes.
Contradicts
Polyphenol assay interference and poor CNS exposure could explain false-positive benefit.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — MAPT
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for MAPT 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 MAPT.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
💰 Estimated Development
Cost
$0
Timeline
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📊 Market Indicators
7d Trend
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Stable
7d Momentum
▼ 0.5%
Volatility
Low
0.0030
Events (7d)
2
Price History
▼10.3%💾 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 iPSC‑derived cortical neurons harboring the MAPT‑P301L mutation are treated with rutin (5 µM) for 5 days THEN a measurable increase in the population of non‑nucleating tau conformers (assessed by a | ≥20% reduction in oligomeric tau concentration (ELISA) and ≥15% increase in the FRET signal reflecting the non‑nucleating conformer. | — no observation — | pending | 0.55 |
| IF recombinant tau K18 (MAPT repeat domain) is incubated with rutin (10 µM) under quiescent conditions THEN a significant reduction in ThT fluorescence (≥30% decrease) will be observed within 2 h rela | ≥30% decrease in ThT fluorescence signal, indicating lowered nucleation of tau oligomers. | — no observation — | pending | 0.65 |
🔮 Falsifiable Predictions (2)
pendingconf 65%
IF recombinant tau K18 (MAPT repeat domain) is incubated with rutin (10 µM) under quiescent conditions THEN a significant reduction in ThT fluorescence (≥30% decrease) will be observed within 2 h relative to vehicle control.
Predicted outcome: ≥30% decrease in ThT fluorescence signal, indicating lowered nucleation of tau oligomers.
Falsification: No significant reduction in ThT fluorescence (≤10% decrease) after rutin treatment, implying rutin does not inhibit tau nucleation.
pendingconf 55%
IF iPSC‑derived cortical neurons harboring the MAPT‑P301L mutation are treated with rutin (5 µM) for 5 days THEN a measurable increase in the population of non‑nucleating tau conformers (assessed by a FRET biosensor) will be detected, leading to a ≥20% reduction in oligomeric tau levels measured by
Predicted outcome: ≥20% reduction in oligomeric tau concentration (ELISA) and ≥15% increase in the FRET signal reflecting the non‑nucleating conformer.
Falsification: No change or increase in oligomeric tau levels (≤5% reduction) and no shift in FRET signal, disproving the conformer stabilization hypothesis.
▸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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