Metabolic Reprogramming of SPP1-Activated Microglia
🧪 Overview
Targeting glycolytic enzymes or promoting oxidative phosphorylation to shift SPP1-activated microglia from destructive to protective phenotypes
Debate provenance: derived from debate `sess_SDA-2026-04-15-gap-pubmed-20260406-062118-e3613755` on question: What molecular mechanisms mediate SPP1-induced microglial phagocytic activation and synaptic targeting?. Consensus signal: domain_expert, skeptic, synthesizer, theorist discussed the mechanism terms HK2, Metabolic, Microglia, Reprogramming, SPP1, SPP1-Activated, phosphorylation. Novelty signal: skeptic-discussed-with-qualified-concession.
🧬 Mechanism
Auto-built from this analysis's top knowledge-graph edges.
graph TD
SPP1["SPP1"] -->|binds to| ITGAV["ITGAV"]
SPP1_1["SPP1"] -->|activates| microglial_activation["microglial_activation"]
microglial_activation_2["microglial_activation"] -->|causes| synaptic_engulfment["synaptic_engulfment"]
SPP1_3["SPP1"] -->|binds to| ITGB3["ITGB3"]
perivascular_macrophages["perivascular_macrophages"] -->|regulates| SPP1_4["SPP1"]
SPP1_5["SPP1"] -->|causes| synaptic_engulfment_6["synaptic_engulfment"]
SPP1_7["SPP1"] -->|risk factor for| neurodegeneration["neurodegeneration"]
SPP1_8["SPP1"] -.->|inhibits| microglial_activation_9["microglial_activation"]
CD44["CD44"] -->|regulates| phagocytic_activation["phagocytic_activation"]
SPP1_10["SPP1"] -->|causes| synapse_loss["synapse_loss"]
SPP1_inhibition["SPP1_inhibition"] -->|prevents| pathological_microglial_a["pathological_microglial_activation"]
ITGAV_inhibition["ITGAV_inhibition"] -->|prevents| synaptic_engulfment_11["synaptic_engulfment"]
style SPP1 fill:#4fc3f7,stroke:#333,color:#000
style ITGAV fill:#4fc3f7,stroke:#333,color:#000
style SPP1_1 fill:#4fc3f7,stroke:#333,color:#000
style microglial_activation fill:#4fc3f7,stroke:#333,color:#000
style microglial_activation_2 fill:#4fc3f7,stroke:#333,color:#000
style synaptic_engulfment fill:#4fc3f7,stroke:#333,color:#000
style SPP1_3 fill:#4fc3f7,stroke:#333,color:#000
style ITGB3 fill:#4fc3f7,stroke:#333,color:#000
style perivascular_macrophages fill:#4fc3f7,stroke:#333,color:#000
style SPP1_4 fill:#4fc3f7,stroke:#333,color:#000
style SPP1_5 fill:#4fc3f7,stroke:#333,color:#000
style synaptic_engulfment_6 fill:#4fc3f7,stroke:#333,color:#000
style SPP1_7 fill:#4fc3f7,stroke:#333,color:#000
style neurodegeneration fill:#ef5350,stroke:#333,color:#000
style SPP1_8 fill:#4fc3f7,stroke:#333,color:#000
style microglial_activation_9 fill:#4fc3f7,stroke:#333,color:#000
style CD44 fill:#4fc3f7,stroke:#333,color:#000
style phagocytic_activation fill:#4fc3f7,stroke:#333,color:#000
style SPP1_10 fill:#4fc3f7,stroke:#333,color:#000
style synapse_loss fill:#4fc3f7,stroke:#333,color:#000
style SPP1_inhibition fill:#4fc3f7,stroke:#333,color:#000
style pathological_microglial_a fill:#4fc3f7,stroke:#333,color:#000
style ITGAV_inhibition fill:#4fc3f7,stroke:#333,color:#000
style synaptic_engulfment_11 fill:#4fc3f7,stroke:#333,color:#000⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — HK2
💉 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 HK2.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
📊 Market Indicators
💾 Resource Usage
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_round_mining
| source | v1_phase_c_backfill |
| origin_type | debate_round_mining |
| _schema_version | 1 |