Metabolic modulators that alter cellular sugar nucleotide pools (like 2-deoxy-D-glucose analogs) could selectively disrupt the aberrant glycosylation patterns on tau vesicles while preserving normal cellular glycosylation, creating a therapeutic window for intervention.
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 curated PDB or AlphaFold mapping for HK1 yet. Search RCSB →
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 HK1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF human iPSC-derived neurons carrying tau mutations are treated with 2-deoxy-D-glucose (2-DG) analog at 500 μM for 72 hours, THEN aberrant sialyl-LewisX glycosylation on tau vesicles will decrease by | Reduction in pathological sialyl-LewisX epitope on isolated tau vesicles (measured by lectin blot or mass spectrometry) by >40% with selectivity ratio >2.5:1 co | — no observation — | pending | 0.25 |
| IF SH-SY5Y cells with doxycycline-inducible mutant tau expression are subjected to HK1 knockdown via siRNA for 48 hours, THEN the abundance of high-mannose N-glycans on purified tau vesicles will decr | Significant reduction in high-mannose N-glycan structures (Man5-Man9 species) on tau vesicles isolated from HK1-knockdown cells, quantified by quantitative glyc | — no observation — | pending | 0.20 |