ID: hyp-SDA-2026-04-08-gap-pubmed-20260406-0
Hypothesis
SPI1-Mediated Metabolic Reprogramming in Neuroinflammation
SPI1 transcriptionally coordinates both inflammatory gene expression and metabolic enzymes in activated microglia, shifting cells toward glycolytic metabolism that sustains chronic neuroinflammation.
EvidencePending (0%)📖 5 cit🗣 1 debates✓ 5 support✗ 3 oppose
✓ All Quality Gates Passed
🧪 Overview
SPI1 transcriptionally coordinates both inflammatory gene expression and metabolic enzymes in activated microglia, shifting cells toward glycolytic metabolism that sustains chronic neuroinflammation. Metabolic modulators targeting SPI1-regulated enzymes could restore homeostatic microglial metabolism.
🧬 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 supports3 contradicts
Supports
Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer's disease-like neuroinflammation and cognitive impairment.
Supports
Spi1 aggravates neuropathic pain by modulating Clec7a-mediated neuroinflammation and microglial phagocytosis.
Supports
Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals.
Supports
Iterative transcription factor screening enables rapid generation of microglia-like cells from human iPSC.
Contradicts
Alzheimer's Disease Genetics: A Dampened Microglial Response?
Contradicts
Late onset Alzheimer's disease genetics implicates microglial pathways in disease risk.
📖 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
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📊 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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