📗 Cite This Artifact
Gut Barrier Permeability-α-Synuclein Axis Modulation
🧪 Overview
Dysbiotic bacteria compromise intestinal barrier integrity through zonulin pathway activation, allowing bacterial antigens and α-synuclein oligomers to enter systemic circulation and seed CNS pathology. Targeted tight junction stabilizers could prevent this peripheral-to-central disease propagation.
🧬 Mechanism
Curated pathway from expert analysis
graph TD
A["Dysbiotic Bacteria<br/>E. coli, gram-negative"]
B["LPS Endotoxin<br/>Release"]
C["TLR4 Activation<br/>Inflammatory Signaling"]
D["MLCK Activation<br/>Phosphorylation"]
E["Tight Junction<br/>Disruption"]
F["CLDN1, OCLN, ZO1<br/>Downregulation"]
G["Gut Barrier<br/>Permeability"]
H["alpha-Synuclein<br/>Aggregation"]
I["Vagal Nerve<br/>Transmission"]
J["CNS alpha-Synuclein<br/>Propagation"]
K["Neurodegeneration<br/>Progression"]
L["Tight Junction<br/>Stabilizers"]
M["Probiotic<br/>Intervention"]
A -->|"produces"| B
B -->|"binds"| C
C -->|"activates"| D
D -->|"phosphorylates"| E
E -->|"reduces"| F
F -->|"increases"| G
G -->|"promotes"| H
H -->|"travels via"| I
I -->|"spreads"| J
J -->|"causes"| K
L -->|"stabilizes"| F
M -->|"restores"| A
style A fill:#ef5350,color:#0d0d1a
style B fill:#ef5350,color:#0d0d1a
style C fill:#ef5350,color:#0d0d1a
style D fill:#ef5350,color:#0d0d1a
style E fill:#ef5350,color:#0d0d1a
style F fill:#ce93d8,color:#0d0d1a
style G fill:#ef5350,color:#0d0d1a
style H fill:#ef5350,color:#0d0d1a
style I fill:#4fc3f7,color:#0d0d1a
style J fill:#ef5350,color:#0d0d1a
style K fill:#ffd54f,color:#0d0d1a
style L fill:#81c784,color:#0d0d1a
style M fill:#81c784,color:#0d0d1a⚖️ Evidence
📙 Related Wiki Pages (15)
🏥 Translation
🧬 3D Protein Structure — CLDN1
No curated PDB or AlphaFold mapping for CLDN1 yet. Search RCSB →
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for CLDN1, OCLN, ZO1, MLCK from GTEx v10.
💉 Clinical Trials (5)Relevance: 44%
Active
Completed
Total Enrolled
Highest Phase
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 CLDN1, OCLN, ZO1, MLCK.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
📊 Market Indicators
💾 Resource Usage
🧭 Related
🔍 Show all 27 edges across 18 relations
associated with (4)
biomarker for (1)
causal extracted (2)
causes (4)
contributes to (1)
contributes to (1)
encodes component (1)
inhibits (2)
maintains (1)
mediates (1)
modulates (1)
promotes (1)
propagates via (1)
protective against (1)
reduces (1)
regulates (1)
therapeutic target for (1)
🗺️ KG Entities (40)
🔗 Dependency Graph (4 upstream, 4 downstream)
🔮 Predictions
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| If hypothesis is true, intervention address the upstream inflammatory triggers while tight junction stabilizers provide direct structural support, potentially achieving superior barrier restoration co | address the upstream inflammatory triggers while tight junction stabilizers provide direct structural support, potentially achieving superior barrier restoratio | — no observation — | pending | 0.60 |
| If hypothesis is true, intervention sequester pathological species in the gut, preventing their systemic dissemination even in the presence of barrier dysfunction | sequester pathological species in the gut, preventing their systemic dissemination even in the presence of barrier dysfunction | — no observation — | pending | 0.60 |
▸Metadata
| status | proposed |
| _schema_version | 1 |
| hypothesis_type | None |
derives from (28)
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🧬 Related Hypotheses — same target / disease (20)
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[Gut Barrier Permeability-α-Synuclein Axis Modulation](http://scidex.ai/artifact/hypothesis-h-6c83282d)
http://scidex.ai/artifact/hypothesis-h-6c83282d