GSK3β-Dependent Tau Phosphorylation Cycling Modulation
🧪 Overview
Develop temporally-controlled GSK3β inhibitors that selectively block pathological tau hyperphosphorylation while preserving physiological phosphorylation cycles. Target the GSK3β-YWHAZ interaction (score: 0.776) to modulate 14-3-3 protein-mediated tau stabilization and prevent propagation-competent phosphorylation patterns.
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 Cycling, Dependent, GSK3B, Modulation, Phosphorylation, YWHAZ, modulation, phosphorylation. 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"]
GSK3B_1["GSK3B"] -->|activates| tau_phosphorylation["tau phosphorylation"]
GSK3B_2["GSK3B"] -->|causes| Neuron_Death["Neuron Death"]
GSK3B_3["GSK3B"] -->|activates| neuron_death["neuron death"]
GSK3B_4["GSK3B"] -->|regulates| catabolic_process["catabolic process"]
GSK3B_5["GSK3B"] -->|causes| Alzheimer_disease["Alzheimer disease"]
style GSK3B fill:#ce93d8,stroke:#333,color:#000
style TAU_Phosphorylation 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 GSK3B_2 fill:#ce93d8,stroke:#333,color:#000
style Neuron_Death 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 GSK3B_4 fill:#ce93d8,stroke:#333,color:#000
style catabolic_process fill:#4fc3f7,stroke:#333,color:#000
style GSK3B_5 fill:#ce93d8,stroke:#333,color:#000
style Alzheimer_disease fill:#ef5350,stroke:#333,color:#000⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — GSK3B
No curated PDB or AlphaFold mapping for GSK3B 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 GSK3B.
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 |