GM1 Ganglioside Reduction via ST3GAL5 Activation to Block Aβ Oligomerization Seeds
Curated pathway from expert analysis
flowchart TD
A["ST3GAL5 Activation<br/>Sialyltransferase upregulation"]
B["GM3 to GD3<br/>Ganglioside Synthesis"]
C["Reduced GM1<br/>Lipid Raft Composition"]
D["Lipid Raft<br/>Reorganization"]
E["BACE1 Activity<br/>Reduction in rafts"]
F["Reduced APP<br/>Amyloidogenic Cleavage"]
G["Fewer Amyloid-beta<br/>Oligomerization Seeds"]
H["Plaque Seeding<br/>Inhibition"]
A --> B
B --> C
C --> D
D --> E
E --> F
F --> G
G --> H
style A fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7
style C fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style H fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for ST3GAL5 yet. Search RCSB →
Median TPM across 13 brain regions for ST3GAL5 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 ST3GAL5.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF ST3GAL5 activation reduces GM1 ganglioside by ≥30% in 5xFAD cortical neurons, THEN Aβ oligomerization seed activity will decrease by ≥50% measured via seed amplification assay, within 96 hours of i | At least 50% reduction in Aβ oligomerization seeds as quantified by thioflavin-T fluorescence or RT-QuIC seed amplification assay | — no observation — | pending | 0.55 |
| IF primary cortical neurons from 5xFAD amyloid model mice are treated with a selective ST3GAL5 agonist (500 nM, 72 hours), THEN GM1 ganglioside levels will decrease by at least 30% compared to vehicle | Significant reduction in GM1 ganglioside levels (≥30% decrease) measured by lipidomics mass spectrometry in neuronal membranes | — no observation — | pending | 0.65 |