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Microbial Metabolite-Mediated α-Synuclein Disaggregation
🧪 Overview
Specific gut bacterial strains produce short-chain fatty acids (SCFAs) that cross the blood-brain barrier and directly modulate α-synuclein aggregation through epigenetic modifications of chaperone proteins. Therapeutic supplementation with SCFA-producing bacteria could prevent or reverse pathological protein aggregation in PD.
🧬 Mechanism
Curated pathway from expert analysis
graph TD
A["Gut Microbiome<br/>B. longum, F. prausnitzii<br/>A. muciniphila"] --> B["SCFA Production<br/>Butyrate, Propionate<br/>Acetate"]
B --> C["Blood-Brain Barrier<br/>Crossing via MCT1/MCT2<br/>Transporters"]
C --> D["HDAC Inhibition<br/>HDAC1, HDAC3, HDAC6<br/>Suppression"]
D --> E["Histone Hyperacetylation<br/>H3/H4 Acetylation<br/>Chromatin Remodeling"]
E --> F["HSF1/NF-Y Transcription<br/>Factor Activation"]
F --> G["HSPA1A Upregulation<br/>Heat Shock Protein 70<br/>Expression"]
C --> H["DNMT1 Inhibition<br/>DNA Methylation<br/>Reduction"]
H --> I["Neuroprotective Gene<br/>Demethylation"]
G --> J["Enhanced Protein<br/>Chaperone Activity"]
I --> J
J --> K["alpha-Synuclein<br/>Disaggregation"]
L["alpha-Synuclein<br/>Pathological Aggregates"] --> K
K --> M["Reduced Neuronal<br/>Toxicity"]
M --> N["Neuroprotection<br/>Disease Modification"]
O["Therapeutic Intervention<br/>SCFA Supplementation<br/>Probiotic Administration"] --> B⚖️ Evidence
📙 Related Wiki Pages (15)
🏥 Translation
🧬 3D Protein Structure — SNCA
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for SNCA, HSPA1A, DNMT1 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 SNCA, HSPA1A, DNMT1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
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🧭 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 (7 upstream, 1 downstream)
🔮 Predictions
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| If hypothesis is true, intervention incorporate engineered bacterial strains with enhanced SCFA production capacity and targeted delivery mechanisms, including synthetic biology approaches to optimize | incorporate engineered bacterial strains with enhanced SCFA production capacity and targeted delivery mechanisms, including synthetic biology approaches to opti | — no observation — | pending | 0.40 |
| If hypothesis is true, intervention integrate pharmacogenomic profiling, microbiome analysis, and metabolomic signatures to optimize strain selection and dosing for individual patients | integrate pharmacogenomic profiling, microbiome analysis, and metabolomic signatures to optimize strain selection and dosing for individual patients | — no observation — | pending | 0.40 |
▸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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[Microbial Metabolite-Mediated α-Synuclein Disaggregation](http://scidex.ai/artifact/hypothesis-h-74777459)
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