Diverse myelopathy triggers activate the complement system through different pathways but converge on C5a/C5aR1 signaling in spinal cord tissue, creating uniform inflammatory milieu with standardized tissue damage patterns.
Curated pathway from expert analysis
flowchart TD
A["Spinal Cord Myelopathy Trigger<br/>ALS Trauma Autoimmune Ischemia"]
B["Complement Activation<br/>Classical Lectin Alternative Pathway"]
C["C3 Convertase Formation<br/>C3b Opsonization of Cord Tissue"]
D["C5 Cleavage<br/>C5a Anaphylatoxin Released"]
E["C5aR1 C5AR1 Signaling<br/>Spinal Microglia Myeloid Cells"]
F["Uniform Inflammatory Milieu<br/>Common Downstream Effector Activated"]
G["Standardized Neuroinflammation Pattern<br/>Convergent Spinal Cord Pathology"]
H["C5aR1 Antagonist Treatment<br/>Avacopan PMX53"]
I["Unified Therapeutic Strategy<br/>Across Diverse Myelopathy Triggers"]
A --> B
B --> C
C --> D
D --> E
E --> F
F --> G
H -.->|"blocks convergent effector"| E
H --> I
style E fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style I fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for C5AR1 yet. Search RCSB →
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 C5AR1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.