Electrostatic bridging by glycans and low-abundance proteins preserves disease-relevant fibril architecture.
Curated pathway from expert analysis
flowchart TD
A["SNCA Alpha-Synuclein<br/>Presynaptic Protein"]
B["SNCA Misfolding<br/>Environmental Stress"]
C["SNCA Oligomers<br/>Toxic Protofibrils"]
D["Mitochondrial Pore<br/>Membrane Disruption"]
E["Lewy Body Formation<br/>Cytoplasmic Inclusions"]
F["Dopaminergic Neuron<br/>Dysfunction/Death"]
G["Nigrostriatal Degeneration<br/>Motor Symptoms"]
H["SNCA A53T/A30P/E46K<br/>Familial PD Mutations"]
A --> B
B --> C
C --> D
C --> E
D --> F
E --> F
F --> G
H -.->|"accelerates"| B
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style C fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style H fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8No linked papers recorded for this hypothesis yet.
Median TPM across 13 brain regions for SNCA 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 SNCA.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF we treat preformed alpha-synuclein fibrils with arylsulfatase A to enzymatically remove sulfated glycans, THEN the fibrils will exhibit reduced thermal stability (Tm decrease >5°C) and altered poly | Decreased fibril thermal stability and loss of disease-relevant polymorph signatures | — no observation — | pending | 0.65 |
| IF we supplement alpha-synuclein fibrillation reactions with physiological concentrations of metal-binding CSF proteins (ceruloplasmin 200 μg/mL, transferrin 300 μg/mL), THEN the resulting fibrils wil | Preserved disease-associated fibril polymorphs with increased protease resistance | — no observation — | pending | 0.55 |