Inflammatory myelopathies converge through activation of shared astrocyte reactivity program controlled by JAK/STAT3 signaling, creating uniform glial scar environment with standardized inflammatory mediator profiles.
Curated pathway from expert analysis
flowchart TD
A["Spinal Cord Injury or Disease<br/>Astrocyte Activation Trigger"]
B["JAK2 STAT3 Pathway Activation<br/>Cytokine-Driven Signaling"]
C["Reactive Astrocyte States<br/>A1 Neurotoxic vs A2 Neuroprotective"]
D["STAT3 Ser727 Phosphorylation<br/>Transcriptional Program Switch"]
E["C3 Lipocalin-2 CXCL10 Upregulated<br/>A1 Neurotoxic Markers"]
F["EAAT2 GLT-1 Glutamate Transporter<br/>Expression Reduced by STAT3"]
G["Glutamate Excitotoxicity<br/>Motor Neuron Vulnerability"]
H["JAK2 Inhibitor Ruxolitinib<br/>STAT3 Decoy Oligonucleotide"]
I["Astrocyte Reactivity Modulated<br/>Neuroprotective Phenotype Favored"]
A --> B
B --> C
C --> D
D --> E
D --> F
F --> G
H -.->|"targets STAT3 convergence"| D
H --> I
style D 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 STAT3 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 STAT3.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.