ID: hyp-SDA-2026-04-08-gap-pubmed-20260406-0
Hypothesis
Neurovascular Unit SPI1 Signaling Hub
SPI1 orchestrates crosstalk between brain endothelial cells, pericytes, and microglia in response to systemic atherosclerosis, creating a neurovascular inflammatory unit.
EvidencePending (0%)📖 5 cit🗣 1 debates✓ 5 support✗ 2 oppose
✓ All Quality Gates Passed
🧪 Overview
SPI1 orchestrates crosstalk between brain endothelial cells, pericytes, and microglia in response to systemic atherosclerosis, creating a neurovascular inflammatory unit. Disrupting SPI1-mediated intercellular signaling could prevent cerebrovascular disease progression to neurodegeneration.
🧬 Mechanism
🔗 Mechanism from KG for SPI1
Auto-built from this analysis's top knowledge-graph edges.
graph TD
SPI1["SPI1"] -->|encodes| PU_1["PU.1"]
SPI1_1["SPI1"] -->|regulates| C1Q["C1Q"]
SPI1_2["SPI1"] -->|contributes to| neuroinflammation["neuroinflammation"]
SPI1_3["SPI1"] -->|regulates| glycolytic_metabolism["glycolytic_metabolism"]
SPI1_4["SPI1"] -->|regulates| microglia["microglia"]
C1Q_5["C1Q"] -->|enhances| SPI1_6["SPI1"]
SPI1_7["SPI1"] -->|causes| neuroinflammatory_memory["neuroinflammatory_memory"]
SPI1_8["SPI1"] -.->|inhibits| synaptic_plasticity["synaptic_plasticity"]
SPI1_9["SPI1"] -->|orchestrates| neurovascular_unit["neurovascular_unit"]
SPI1_10["SPI1"] -->|amplifies| neuroinflammation_11["neuroinflammation"]
SPI1_12["SPI1"] -->|modulates| chromatin_accessibility["chromatin_accessibility"]
chronic_vascular_inflamma["chronic_vascular_inflammation"] -->|regulates| SPI1_13["SPI1"]
SPI1_14["SPI1"] -->|maintains| microglial_activation["microglial_activation"]
SPI1_15["SPI1"] -->|associated with| atherosclerosis["atherosclerosis"]
SPI1_16["SPI1"] -->|regulates| Inflammatory_gene_express["Inflammatory gene expression"]
style SPI1 fill:#ce93d8,stroke:#333,color:#000
style PU_1 fill:#4fc3f7,stroke:#333,color:#000
style SPI1_1 fill:#ce93d8,stroke:#333,color:#000
style C1Q fill:#ce93d8,stroke:#333,color:#000
style SPI1_2 fill:#ce93d8,stroke:#333,color:#000
style neuroinflammation fill:#4fc3f7,stroke:#333,color:#000
style SPI1_3 fill:#ce93d8,stroke:#333,color:#000
style glycolytic_metabolism fill:#81c784,stroke:#333,color:#000
style SPI1_4 fill:#ce93d8,stroke:#333,color:#000
style microglia fill:#4fc3f7,stroke:#333,color:#000
style C1Q_5 fill:#ce93d8,stroke:#333,color:#000
style SPI1_6 fill:#ce93d8,stroke:#333,color:#000
style SPI1_7 fill:#ce93d8,stroke:#333,color:#000
style neuroinflammatory_memory fill:#4fc3f7,stroke:#333,color:#000
style SPI1_8 fill:#ce93d8,stroke:#333,color:#000
style synaptic_plasticity fill:#4fc3f7,stroke:#333,color:#000
style SPI1_9 fill:#ce93d8,stroke:#333,color:#000
style neurovascular_unit fill:#4fc3f7,stroke:#333,color:#000
style SPI1_10 fill:#ce93d8,stroke:#333,color:#000
style neuroinflammation_11 fill:#4fc3f7,stroke:#333,color:#000
style SPI1_12 fill:#ce93d8,stroke:#333,color:#000
style chromatin_accessibility fill:#4fc3f7,stroke:#333,color:#000
style chronic_vascular_inflamma fill:#4fc3f7,stroke:#333,color:#000
style SPI1_13 fill:#ce93d8,stroke:#333,color:#000
style SPI1_14 fill:#ce93d8,stroke:#333,color:#000
style microglial_activation fill:#4fc3f7,stroke:#333,color:#000
style SPI1_15 fill:#ce93d8,stroke:#333,color:#000
style atherosclerosis fill:#ef5350,stroke:#333,color:#000
style SPI1_16 fill:#ce93d8,stroke:#333,color:#000
style Inflammatory_gene_express fill:#4fc3f7,stroke:#333,color:#000⚖️ Evidence
⚖️ Evidence Matrix5 supports0 contradicts
Supports
Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer's disease-like neuroinflammation and cognitive impairment.
Supports
A novel molecular class that recruits HDAC/MECP2 complexes to PU.1 motifs reduces neuroinflammation.
Supports
Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology.
Supports
SPI1 triggers the formation of neutrophil extracellular traps in multiple sclerosis through CXCL4.
Supports
Revealing the nervous system requirements of Alzheimer disease risk genes in Drosophila.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — SPI1
No curated PDB or AlphaFold mapping for SPI1 yet. Search RCSB →
💉 Clinical Trials
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 SPI1.
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
0.0530
Events (7d)
0
Price History
▲5.8%💾 Resource Usage
LLM Tokens
10,898
$0.0654
Total Cost
$0.0654
▸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
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