NETs-MMP-Wnt Axis Therapeutic Cascade
🧪 Overview
Triple-target therapy combining PAD4 inhibitors to block neutrophil extracellular trap formation, selective MMP inhibitors, and Wnt pathway activators to synergistically restore BBB integrity
Debate provenance: derived from debate `sess_SDA-2026-04-16-gap-bbb-tjp-20260416041707` on question: Blood-brain barrier tight junction disruption by neuroinflammatory cytokines. Consensus signal: clinical_trialist, computational_biologist, domain_expert, epidemiologist, skeptic, synthesizer, theorist discussed the mechanism terms BBB, Cascade, MMP, NETs-MMP-Wnt, PAD4, Therapeutic. Novelty signal: skeptic-discussed-with-qualified-concession.
🧬 Mechanism
Auto-built from this analysis's top knowledge-graph edges.
graph TD
TJP1["TJP1"] -->|interacts with con| CLDN5["CLDN5"]
OCLN["OCLN"] -->|interacts with con| CLDN5_1["CLDN5"]
CTNNB1["CTNNB1"] -->|interacts with con| TJP1_2["TJP1"]
CTNNB1_3["CTNNB1"] -->|interacts with con| OCLN_4["OCLN"]
diseases_corticobasal_deg["diseases-corticobasal-degeneration"] -->|investigated in| h_b2aeabb1["h-b2aeabb1"]
diseases_machado_joseph_d["diseases-machado-joseph-disease"] -->|investigated in| h_b2aeabb1_5["h-b2aeabb1"]
genes_rpl30["genes-rpl30"] -->|investigated in| h_b2aeabb1_6["h-b2aeabb1"]
IL1B["IL1B"] -->|increases| BBB_permeability["BBB_permeability"]
NET_formation["NET_formation"] -->|activates| MMP9["MMP9"]
MMP9_7["MMP9"] -->|degrades| tight_junction_proteins["tight_junction_proteins"]
TNF["TNF"] -->|increases| BBB_permeability_8["BBB_permeability"]
TJP1_9["TJP1"] -->|protective against| BBB_integrity["BBB_integrity"]
style TJP1 fill:#ce93d8,stroke:#333,color:#000
style CLDN5 fill:#ce93d8,stroke:#333,color:#000
style OCLN fill:#ce93d8,stroke:#333,color:#000
style CLDN5_1 fill:#ce93d8,stroke:#333,color:#000
style CTNNB1 fill:#ce93d8,stroke:#333,color:#000
style TJP1_2 fill:#ce93d8,stroke:#333,color:#000
style CTNNB1_3 fill:#ce93d8,stroke:#333,color:#000
style OCLN_4 fill:#ce93d8,stroke:#333,color:#000
style diseases_corticobasal_deg fill:#ef5350,stroke:#333,color:#000
style h_b2aeabb1 fill:#4fc3f7,stroke:#333,color:#000
style diseases_machado_joseph_d fill:#ef5350,stroke:#333,color:#000
style h_b2aeabb1_5 fill:#4fc3f7,stroke:#333,color:#000
style genes_rpl30 fill:#ce93d8,stroke:#333,color:#000
style h_b2aeabb1_6 fill:#4fc3f7,stroke:#333,color:#000
style IL1B fill:#ce93d8,stroke:#333,color:#000
style BBB_permeability fill:#4fc3f7,stroke:#333,color:#000
style NET_formation fill:#4fc3f7,stroke:#333,color:#000
style MMP9 fill:#ce93d8,stroke:#333,color:#000
style MMP9_7 fill:#ce93d8,stroke:#333,color:#000
style tight_junction_proteins fill:#4fc3f7,stroke:#333,color:#000
style TNF fill:#ce93d8,stroke:#333,color:#000
style BBB_permeability_8 fill:#4fc3f7,stroke:#333,color:#000
style TJP1_9 fill:#4fc3f7,stroke:#333,color:#000
style BBB_integrity fill:#4fc3f7,stroke:#333,color:#000⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
💉 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 this gene.
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 |