Rutin engages exposed tau aggregation motifs and lowers early oligomer nucleation, with strongest support expected from cell-free seeding and structural footprinting assays.
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:#ef9a9aNo linked papers recorded for this hypothesis yet.
Median TPM across 13 brain regions for MAPT 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 MAPT.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| 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 |