Curated pathway from expert analysis
flowchart TD
A["TREM2 Receptor Activation<br/>Amyloid and Lipid Ligand Binding"]
B["TYROBP DAP12 Adaptor Protein<br/>Plasma Membrane TREM2 Anchoring"]
C["ITAM Phosphorylation<br/>SYK Kinase Recruitment"]
D["SYK Downstream Signaling<br/>PLCgamma PI3K Akt Cascade"]
E["Microglial Survival Phagocytosis<br/>Lipid Metabolism Program"]
F["AD ALS Pathology Reduces TYROBP<br/>Signaling Scaffold Destabilized"]
G["Selective TYROBP Stabilization<br/>Protein Stability Enhancement Strategy"]
H["SYK Activity Maintained<br/>Neuroprotective Signaling Restored"]
A --> B
B --> C
C --> D
D --> E
F -.->|"disrupts"| B
G --> B
G --> H
H --> E
style B 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 ['TYROBP' yet. Search RCSB →
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 ['TYROBP', 'SYK'].
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF primary murine microglia are treated with a TYROBP stabilizer (e.g., small molecule or viral TYROBP overexpression) for 48 hours, THEN phospho-SYK (p-SYK) levels will increase by at least 50% compa | Increased SYK phosphorylation (p-SYK/total SYK ratio) as measured by western blot or phospho-flow cytometry, along with upregulated expression of downstream neu | — no observation — | pending | 0.75 |
| IF 5xFAD amyloid mice (3 months old) receive intracranial AAV-mediated TYROBP overexpression in hippocampus for 8 weeks, THEN amyloid plaque-associated microglia will show enhanced SYK activation and | Increased p-SYK intensity in Iba1+ plaque-associated microglia (measured by immunohistochemistry quantification) and decreased pro-inflammatory gene expression | — no observation — | pending | 0.72 |