Prion-Like Domain Stabilizers via Aromatic Interaction Modulators
🧪 Overview
Compounds targeting the low-complexity aromatic-rich kinked segments (LARKS) in TDP-43's prion-like domain could prevent pathological amyloid transition while preserving physiological phase separation. These would act as molecular stabilizers of the native LARKS conformation.
Debate provenance: derived from debate `sess_sda-2026-04-01-gap-006` on question: TDP-43 undergoes liquid-liquid phase separation that becomes pathological. Small molecules targeting phase separation properties could be therapeutic but the design principles are undefined.. Consensus signal: clinical_trialist, domain_expert, medicinal_chemist, skeptic, synthesizer, theorist discussed the mechanism terms Aromatic, Domain, Interaction, LARKS, Modulators, Prion-Like, Stabilizers, TARDBP. Novelty signal: skeptic-discussed-with-qualified-concession.
🧬 Mechanism
Auto-built from this analysis's top knowledge-graph edges.
graph TD
TARDBP["TARDBP"] -->|associated with| neurodegeneration["neurodegeneration"]
TARDBP_1["TARDBP"] -->|participates in| TDP_43_RNA_processing___p["TDP-43 RNA processing / phase separation"]
TGM2["TGM2"] -->|co discussed| TARDBP_2["TARDBP"]
TARDBP_3["TARDBP"] -->|co discussed| PRMT1["PRMT1"]
TARDBP_4["TARDBP"] -->|co discussed| PARP1["PARP1"]
TARDBP_5["TARDBP"] -->|co discussed| HSPA1A["HSPA1A"]
TARDBP_6["TARDBP"] -->|co discussed| G3BP1["G3BP1"]
TARDBP_7["TARDBP"] -->|co discussed| SRPK1["SRPK1"]
PRMT1_8["PRMT1"] -->|co discussed| TARDBP_9["TARDBP"]
HSPA1A_10["HSPA1A"] -->|co discussed| TARDBP_11["TARDBP"]
G3BP1_12["G3BP1"] -->|co discussed| TARDBP_13["TARDBP"]
SRPK1_14["SRPK1"] -->|co discussed| TARDBP_15["TARDBP"]
PARP1_16["PARP1"] -->|co discussed| TARDBP_17["TARDBP"]
HSPA1A_18["HSPA1A"] -->|co associated with| TARDBP_19["TARDBP"]
PRMT1_20["PRMT1"] -->|co associated with| TARDBP_21["TARDBP"]
style TARDBP fill:#ce93d8,stroke:#333,color:#000
style neurodegeneration fill:#ef5350,stroke:#333,color:#000
style TARDBP_1 fill:#ce93d8,stroke:#333,color:#000
style TDP_43_RNA_processing___p fill:#81c784,stroke:#333,color:#000
style TGM2 fill:#ce93d8,stroke:#333,color:#000
style TARDBP_2 fill:#ce93d8,stroke:#333,color:#000
style TARDBP_3 fill:#ce93d8,stroke:#333,color:#000
style PRMT1 fill:#ce93d8,stroke:#333,color:#000
style TARDBP_4 fill:#ce93d8,stroke:#333,color:#000
style PARP1 fill:#ce93d8,stroke:#333,color:#000
style TARDBP_5 fill:#ce93d8,stroke:#333,color:#000
style HSPA1A fill:#ce93d8,stroke:#333,color:#000
style TARDBP_6 fill:#ce93d8,stroke:#333,color:#000
style G3BP1 fill:#ce93d8,stroke:#333,color:#000
style TARDBP_7 fill:#ce93d8,stroke:#333,color:#000
style SRPK1 fill:#ce93d8,stroke:#333,color:#000
style PRMT1_8 fill:#ce93d8,stroke:#333,color:#000
style TARDBP_9 fill:#ce93d8,stroke:#333,color:#000
style HSPA1A_10 fill:#ce93d8,stroke:#333,color:#000
style TARDBP_11 fill:#ce93d8,stroke:#333,color:#000
style G3BP1_12 fill:#ce93d8,stroke:#333,color:#000
style TARDBP_13 fill:#ce93d8,stroke:#333,color:#000
style SRPK1_14 fill:#ce93d8,stroke:#333,color:#000
style TARDBP_15 fill:#ce93d8,stroke:#333,color:#000
style PARP1_16 fill:#ce93d8,stroke:#333,color:#000
style TARDBP_17 fill:#ce93d8,stroke:#333,color:#000
style HSPA1A_18 fill:#ce93d8,stroke:#333,color:#000
style TARDBP_19 fill:#ce93d8,stroke:#333,color:#000
style PRMT1_20 fill:#ce93d8,stroke:#333,color:#000
style TARDBP_21 fill:#ce93d8,stroke:#333,color:#000⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — TARDBP
💉 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 TARDBP.
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 |