Synthetic glycan mimetics that competitively bind to tau vesicle surface receptors could prevent pathological vesicle fusion and tau spreading between neurons. These molecular decoys would act as competitive inhibitors of disease progression.
Auto-built from this analysis's top knowledge-graph edges.
graph TD
HK1["HK1"] -->|participates in| glucose_metabolism["glucose_metabolism"]
ST6GAL1["ST6GAL1"] -->|regulates| sialylation["sialylation"]
MAPT["MAPT"] -->|participates in| vesicle_transport["vesicle_transport"]
ST6GAL1_1["ST6GAL1"] -->|catalyzes| sialylation_2["sialylation"]
LGALS3["LGALS3"] -->|regulates| autophagy["autophagy"]
MGAT5["MGAT5"] -->|catalyzes| N_glycosylation["N_glycosylation"]
glycan_patterns["glycan_patterns"] -->|characterizes| tau_vesicles["tau_vesicles"]
n2_deoxy_D_glucose_analogs["2-deoxy-D-glucose analogs"] -->|disrupts| glycosylation_patterns["glycosylation patterns"]
LGALS3_3["LGALS3"] -->|targets| tau_vesicles_4["tau_vesicles"]
MGAT5_5["MGAT5"] -->|marks| tau_vesicles_6["tau_vesicles"]
NEU1["NEU1"] -.->|inhibits| tau_aggregation["tau_aggregation"]
synthetic_glycan_mimetics["synthetic_glycan_mimetics"] -.->|inhibits| tau_spreading["tau_spreading"]
style HK1 fill:#ce93d8,stroke:#333,color:#000
style glucose_metabolism fill:#81c784,stroke:#333,color:#000
style ST6GAL1 fill:#ce93d8,stroke:#333,color:#000
style sialylation fill:#ffd54f,stroke:#333,color:#000
style MAPT fill:#ce93d8,stroke:#333,color:#000
style vesicle_transport fill:#4fc3f7,stroke:#333,color:#000
style ST6GAL1_1 fill:#ce93d8,stroke:#333,color:#000
style sialylation_2 fill:#4fc3f7,stroke:#333,color:#000
style LGALS3 fill:#ce93d8,stroke:#333,color:#000
style autophagy fill:#4fc3f7,stroke:#333,color:#000
style MGAT5 fill:#ce93d8,stroke:#333,color:#000
style N_glycosylation fill:#4fc3f7,stroke:#333,color:#000
style glycan_patterns fill:#4fc3f7,stroke:#333,color:#000
style tau_vesicles fill:#4fc3f7,stroke:#333,color:#000
style n2_deoxy_D_glucose_analogs fill:#4fc3f7,stroke:#333,color:#000
style glycosylation_patterns fill:#4fc3f7,stroke:#333,color:#000
style LGALS3_3 fill:#4fc3f7,stroke:#333,color:#000
style tau_vesicles_4 fill:#4fc3f7,stroke:#333,color:#000
style MGAT5_5 fill:#ce93d8,stroke:#333,color:#000
style tau_vesicles_6 fill:#4fc3f7,stroke:#333,color:#000
style NEU1 fill:#ce93d8,stroke:#333,color:#000
style tau_aggregation fill:#4fc3f7,stroke:#333,color:#000
style synthetic_glycan_mimetics fill:#4fc3f7,stroke:#333,color:#000
style tau_spreading fill:#4fc3f7,stroke:#333,color:#000No linked papers recorded for this hypothesis yet.
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 synthetic glycan decoys (at concentrations of 10-50 μM) are applied to primary hippocampal neurons transduced with P301S tau and challenged with pathological tau seed-containing extracellular vesic | Significant reduction in extracellular tau burden measured by ELISA (total tau and phosphorylated tau-231/396 epitopes), with >40% decrease in tau seed activity | — no observation — | pending | 0.65 |
| IF rTg4510 tau transgenic mice receive intraperitoneal injections of glycan decoys (10 mg/kg, 3x/week) beginning at 2 months of age, THEN survival will be extended by >25% and rotarod performance will | Median survival increased from ~5.5 months (historical vehicle) to >6.8 months; latency to fall on accelerating rotarod (4-40 RPM over 5 min) improved by >30% a | — no observation — | pending | 0.55 |