SIRPA antagonism to enhance microglial activation through removal of inhibitory CD47-SIRPA signaling
Curated pathway from expert analysis
flowchart TD
A["CD47 Expression on Neurons and Plaques<br/>Anti-Phagocytic Do Not Eat Me Signal"]
B["SIRPA Receptor on Microglia<br/>Inhibitory Immunoreceptor"]
C["CD47-SIRPA Interaction<br/>Microglial Phagocytosis Suppressed"]
D["Amyloid and Debris Accumulate<br/>Clearance Impaired in Disease"]
E["SIRPA Antagonist Treatment<br/>Removes CD47-Mediated Inhibition"]
F["Microglial Phagocytic Activation<br/>Disinhibition of Clearance"]
G["Amyloid Plaque Burden Reduced<br/>Neuroinflammation Resolved"]
H["AD Neuroprotective Outcome<br/>Cognitive Preservation"]
A --> B
B --> C
C --> D
E -.->|"blocks inhibitory signal"| C
E --> F
F --> G
G --> H
style C fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style H fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for ['SIRPA'] 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 ['SIRPA'].
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF anti-SIRPA antibody (10 mg/kg, i.p., every 3 days) is administered to 5xFAD transgenic mice for 4 weeks, THEN amyloid plaque burden will decrease by ≥30% in the hippocampus compared to vehicle-trea | Congo red+ plaque area decreases ≥30% in hippocampus; Iba1+ microglia show hypertrophic morphology (somatic area ≥150% of control); CD68+ microglial coverage ar | — no observation — | pending | 0.72 |
| IF primary mouse microglia are treated with SIRPA-blocking antibody (500 µg/mL) for 48 hours, THEN cell surface CD86 and CD68 expression will increase by ≥50% compared to isotype control, using cultur | CD86 MFI increases from baseline ~200 to ≥300; CD68+ area increases ≥50% via confocal morphometry; phagocytosis of fluorescent E. coli bioparticles increases ≥4 | — no observation — | pending | 0.78 |