🧪
hypothesis

Microglial SPI1 Priming by Circulating C1Q

Hypothesis

Microglial SPI1 Priming by Circulating C1Q

Circulating C1Q from atherosclerotic plaques crosses a compromised blood-brain barrier and primes microglial SPI1 expression, creating neuroinflammatory memory that predisposes to neurodegeneration.
🧬 C1Q🩺 neuroinflammation🎯 Composite 46%💱 $0.52▲5.8%active
EvidencePending (0%)📖 5 cit🗣 1 debates 5 support 3 oppose
✓ All Quality Gates Passed
Mechanistic 0.50 (15%) Evidence 0.50 (15%) Novelty 0.50 (12%) Feasibility 0.50 (12%) Impact 0.00 (12%) Druggability 0.50 (10%) Safety 0.50 (8%) Competition 0.50 (6%) Data Avail. 0.50 (5%) Reproducible 0.50 (5%) KG Connect 0.30 (8%) 0.455 composite
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Composite46%

🧪 Overview

Circulating C1Q from atherosclerotic plaques crosses a compromised blood-brain barrier and primes microglial SPI1 expression, creating neuroinflammatory memory that predisposes to neurodegeneration. Anti-C1Q biologics could prevent this vascular-to-brain inflammatory transmission.

🧬 Mechanism

🔗 Mechanism from KG for C1Q

Auto-built from this analysis's top knowledge-graph edges.

graph TD
    C1Q["C1Q"] -->|participates in| complement_cascade["complement_cascade"]
    SPI1["SPI1"] -->|regulates| C1Q_1["C1Q"]
    C1Q_2["C1Q"] -->|crosses| blood_brain_barrier["blood-brain_barrier"]
    C1Q_3["C1Q"] -->|enhances| SPI1_4["SPI1"]
    C1q["C1q"] -->|activates| microglial_SPI1_expressio["microglial SPI1 expression"]
    style C1Q fill:#ce93d8,stroke:#333,color:#000
    style complement_cascade fill:#81c784,stroke:#333,color:#000
    style SPI1 fill:#ce93d8,stroke:#333,color:#000
    style C1Q_1 fill:#ce93d8,stroke:#333,color:#000
    style C1Q_2 fill:#ce93d8,stroke:#333,color:#000
    style blood_brain_barrier fill:#4fc3f7,stroke:#333,color:#000
    style C1Q_3 fill:#ce93d8,stroke:#333,color:#000
    style SPI1_4 fill:#ce93d8,stroke:#333,color:#000
    style C1q fill:#4fc3f7,stroke:#333,color:#000
    style microglial_SPI1_expressio fill:#4fc3f7,stroke:#333,color:#000

⚖️ Evidence

⚖️ Evidence Matrix5 supports3 contradicts
Supports
A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis.
Nature2021PMID:34497421medium
Supports
Roles of neuropathology-associated reactive astrocytes: a systematic review.
Acta Neuropathol Commun2023PMID:36915214medium
Supports
Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer's disease mouse models.
Nat Aging2022PMID:37118504medium
Supports
The neuronal pentraxin Nptx2 regulates complement activity and restrains microglia-mediated synapse loss in neurodegeneration.
Sci Transl Med2023PMID:36989373medium
Supports
TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration.
Immunity2023PMID:37442133medium
Contradicts
Roles of neuropathology-associated reactive astrocytes: a systematic review.
Acta Neuropathol Commun2023PMID:36915214medium
Contradicts
Microglia regulation of synaptic plasticity and learning and memory.
Neural Regen Res2022PMID:34472455medium
Contradicts
Microglial TYROBP/DAP12 in Alzheimer's disease: Transduction of physiological and pathological signals across TREM2.
Mol Neurodegener2022PMID:36002854medium
📖 Linked Papers

No linked papers recorded for this hypothesis yet.

🏥 Translation

🧬 3D Protein Structure — C1Q

No curated PDB or AlphaFold mapping for C1Q 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.

🔍 Search ClinVar for C1Q →

No DepMap CRISPR Chronos data found for C1Q.

Run python3 scripts/backfill_hypothesis_depmap.py to populate.

🏆 Tournament

🏆 Arenas / Elo

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📊 Market Indicators

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💾 Resource Usage

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