Synaptic VDAC1-Mediated Mitochondrial Tau Trafficking
🧪 Overview
Target VDAC1's interaction with tau (score: 0.963) to prevent mitochondrial dysfunction-induced tau release. Develop VDAC1 modulators that maintain mitochondrial integrity while blocking pathological tau translocation across mitochondrial membranes, reducing both tau propagation and neuronal vulnerability.
Debate provenance: derived from debate `sess_SDA-2026-04-02-gap-tau-prop-20260402003221` on question: Investigate prion-like spreading of tau pathology through connected brain regions, focusing on trans-synaptic transfer, extracellular vesicle-mediated spread, and intervention strategies at each propagation step. Consensus signal: domain_expert, skeptic, synthesizer, theorist discussed the mechanism terms Mitochondrial, Synaptic, Trafficking, VDAC1, VDAC1-Mediated, mitochondrial, synaptic. Novelty signal: skeptic-discussed-with-qualified-concession.
🧬 Mechanism
Auto-built from this analysis's top knowledge-graph edges.
graph TD
GSK3B["GSK3B"] -->|regulates| TAU_Phosphorylation["TAU Phosphorylation"]
FYN["FYN"] -->|associated with| SYNAPTIC_FUNCTION["SYNAPTIC_FUNCTION"]
GSK3B_1["GSK3B"] -->|activates| tau_phosphorylation["tau phosphorylation"]
FYN_2["FYN"] -->|regulates| synaptic_function["synaptic function"]
tau_protein["tau protein"] -->|causes| neurodegeneration["neurodegeneration"]
GSK3B_3["GSK3B"] -->|causes| Neuron_Death["Neuron Death"]
FYN_4["FYN"] -->|regulates| MAPT["MAPT"]
FYN_5["FYN"] -->|regulates| memory_formation["memory formation"]
APOE["APOE"] -->|regulates| Tau_Propagation["Tau Propagation"]
apoe4["apoe4"] -->|enhances| Tau_Propagation_6["Tau Propagation"]
VDAC1["VDAC1"] -->|regulates| MAPT_7["MAPT"]
APOE_8["APOE"] -->|associated with| amyloid_beta_complex["amyloid-beta complex"]
style GSK3B fill:#ce93d8,stroke:#333,color:#000
style TAU_Phosphorylation fill:#4fc3f7,stroke:#333,color:#000
style FYN fill:#ce93d8,stroke:#333,color:#000
style SYNAPTIC_FUNCTION fill:#4fc3f7,stroke:#333,color:#000
style GSK3B_1 fill:#ce93d8,stroke:#333,color:#000
style tau_phosphorylation fill:#4fc3f7,stroke:#333,color:#000
style FYN_2 fill:#4fc3f7,stroke:#333,color:#000
style synaptic_function fill:#4fc3f7,stroke:#333,color:#000
style tau_protein fill:#4fc3f7,stroke:#333,color:#000
style neurodegeneration fill:#4fc3f7,stroke:#333,color:#000
style GSK3B_3 fill:#ce93d8,stroke:#333,color:#000
style Neuron_Death fill:#4fc3f7,stroke:#333,color:#000
style FYN_4 fill:#ce93d8,stroke:#333,color:#000
style MAPT fill:#ce93d8,stroke:#333,color:#000
style FYN_5 fill:#ce93d8,stroke:#333,color:#000
style memory_formation fill:#4fc3f7,stroke:#333,color:#000
style APOE fill:#ce93d8,stroke:#333,color:#000
style Tau_Propagation fill:#4fc3f7,stroke:#333,color:#000
style apoe4 fill:#ef5350,stroke:#333,color:#000
style Tau_Propagation_6 fill:#4fc3f7,stroke:#333,color:#000
style VDAC1 fill:#ce93d8,stroke:#333,color:#000
style MAPT_7 fill:#ce93d8,stroke:#333,color:#000
style APOE_8 fill:#ce93d8,stroke:#333,color:#000
style amyloid_beta_complex fill:#4fc3f7,stroke:#333,color:#000⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — VDAC1
No curated PDB or AlphaFold mapping for VDAC1 yet. Search RCSB →
💉 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 VDAC1.
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 |