CCL2-CCR2 myeloid signaling as a selective driver of fast-fatigable motor-neuron denervation as proximal driver in CCL2-CCR2 Axis at NMJ: Mechanism of Selective Motor Neuron Vulnerability in ALS
🧪 Overview
CCL2-CCR2 myeloid signaling as a selective driver of fast-fatigable motor-neuron denervation should produce a measurable proximal phenotype before late disease pathology. The decisive test is myeloid-specific CCR2 blockade with fast/slow motor-unit stratification and NMJ integrity measurements.
🧬 Mechanism
Curated pathway from expert analysis
flowchart TD
A["CCL2 Chemokine Secretion<br/>Denervated Muscle and Schwann Cells"]
B["CCR2 Receptor Upregulation<br/>Pro-inflammatory Macrophages"]
C["CX3CR1/CCR2 Monocyte Recruitment<br/>NMJ Neuromuscular Junction"]
D["Fast-Fatigable Motor Neuron<br/>Synapse Stripping Begins"]
E[" neuromuscular Dependency<br/>Sustained Jnk/c-Jun Signaling"]
F["Denervation and Axonal Degeneration<br/>ALS Disease Progression"]
A --> B
B --> C
C --> D
D --> E
E --> F
style A fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — CCL2-CCR2
No curated PDB or AlphaFold mapping for CCL2-CCR2 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 CCL2-CCR2.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
📊 Market Indicators
💾 Resource Usage
No resource usage or linked notebooks recorded for this hypothesis yet.
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesizer
| source | v1_phase_c_backfill |
| origin_type | debate_synthesizer |
| _schema_version | 1 |