ID: hyp-sda-2026-04-01-001-5
Hypothesis
SIRPA-Mediated Microglial Disinhibition
SIRPA antagonism to enhance microglial activation through removal of inhibitory CD47-SIRPA signaling.
EvidencePending (0%)📖 5 cit🗣 1 debates✓ 5 support✗ 1 oppose
✓ All Quality Gates Passed
🧪 Overview
SIRPA antagonism to enhance microglial activation through removal of inhibitory CD47-SIRPA signaling
🧬 Mechanism
🧬 Curated Mechanism Pathway
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:#a5d6a7⚖️ Evidence
⚖️ Evidence Matrix5 supports0 contradicts
Supports
Microglia regulation of synaptic plasticity and learning and memory.
Supports
Lactate reprograms glioblastoma immunity through CBX3-regulated histone lactylation.
Supports
CD47 Protects Synapses from Excess Microglia-Mediated Pruning during Development.
Supports
CD47 signaling induces hepatic cell death and microglia activation during hepatic encephalopathy.
Supports
Engineered Bacterial Outer Membrane Vesicles-Based Doxorubicin and CD47-siRNA Co-Delivery Nanoplatform Overcomes Immune Resistance to Potentiate the Immunotherapy of Glioblastoma.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — ['SIRPA']
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.
🏆 Tournament
🏆 Arenas / Elo
No arena matches recorded yet. Browse Arenas →
📊 Market Indicators
7d Trend
↔
Stable
7d Momentum
▲ 0.0%
Volatility
High
0.0580
Events (7d)
1
Price History
▼8.2%💾 Resource Usage
LLM Tokens
14,692
$0.0882
Total Cost
$0.0882
🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| 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 |
🔮 Falsifiable Predictions (2)
pendingconf 78%
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 cultured primary microglia from C57BL/6 mice.
Predicted outcome: CD86 MFI increases from baseline ~200 to ≥300; CD68+ area increases ≥50% via confocal morphometry; phagocytosis of fluorescent E. coli bioparticles in
Falsification: No significant change (<20% increase) in CD68/CD86 expression or phagocytic index after SIRPA blockade would refute the hypothesis that SIRPA antagonism disinhibits microglial activation
pendingconf 72%
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-treated controls, using 5xFAD APP/PS1 mice at 6 months of age.
Predicted outcome: Congo red+ plaque area decreases ≥30% in hippocampus; Iba1+ microglia show hypertrophic morphology (somatic area ≥150% of control); CD68+ microglial c
Falsification: No reduction in amyloid burden or failure to observe morphologically activated microglia after SIRPA antagonist treatment would disprove the hypothesis that SIRPA blockade enhances microglial-mediated
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesis
| source | v1_phase_c_backfill |
| origin_type | debate_synthesis |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
Public annotations (0)Annotate on Hypothes.is →
No public annotations yet.