🧪
hypothesis

TDP-43 phase-separation and nuclear-function failure in ALS/FTD

Hypothesis

TDP-43 phase-separation and nuclear-function failure in ALS/FTD

Pathological TDP-43 condensate dynamics, phosphorylation, aggregation, and nuclear depletion disrupt RNA processing in ALS/FTD.
🧬 TARDBP; TIA1🩺 neurodegeneration🎯 Composite 69%💱 $0.58▼15.4%proposed
EvidencePending (0%)📖 0 cit🗣 1 debates✓ 4 support✗ 2 oppose
✓ All Quality Gates Passed
☰ Compare⚔️ Duel⚛️ Collide
📄 Export LaTeX
arXiv PreprintNeurIPSNature MethodsPLOS ONE
📖 Export BibTeXinteract with this hypothesis
Composite69%

🧪 Overview

Pathological TDP-43 condensate dynamics, phosphorylation, aggregation, and nuclear depletion disrupt RNA processing in ALS/FTD. The strongest therapeutic version is not generic LLPS modulation but restoration of nuclear TDP-43 function, cryptic-exon repression, stress-granule resolution, and neuronal survival in human-relevant models.

🧬 Mechanism

No curated mechanism pathway recorded for this hypothesis.

⚖️ Evidence

⚖️ Evidence Matrix4 supports2 contradicts
Supports
TDP-43 pathology is present in most ALS cases and many FTD cases, giving the mechanism strong disease relevance.
PMID:29238078
Supports
ALS-linked TARDBP mutations alter phase-separation and aggregation properties.
PMID:28453719
Supports
Patient-derived motor neurons show stress-granule and TDP-43-related abnormalities relevant to therapeutic testing.
PMID:31542276
Supports
Cryptic-exon biomarkers provide a plausible pharmacodynamic readout for TDP-43 loss of nuclear function.
PMID:38278991
Contradicts
TDP-43 inclusions may be late-stage correlates, and LLPS changes may not be the rate-limiting toxic mechanism compared with cryptic splicing, RNA transport, mitochondrial effects, or cytoplasmic toxicity.
PMID:29238078
Contradicts
Restoring liquid-like condensate behavior alone may fail if nuclear localization, cryptic-exon repression, neuronal survival, or axonal RNA transport are not rescued.
PMID:28453719
📖 Linked Papers

No linked papers recorded for this hypothesis yet.

🏥 Translation

🧬 3D Protein Structure — TARDBP;

No curated PDB or AlphaFold mapping for TARDBP; 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.

🔍 Search ClinVar for TARDBP; TIA1 →

No DepMap CRISPR Chronos data found for TARDBP; TIA1.

Run python3 scripts/backfill_hypothesis_depmap.py to populate.

🏆 Tournament

🏆 Arenas / Elo

No arena matches recorded yet. Browse Arenas →

📊 Market Indicators

7d Trend
↘
Falling
7d Momentum
▼ 1.0%
Volatility
Low
0.0024
Events (7d)
3
Price History
▼15.4%

💾 Resource Usage

No resource usage or linked notebooks recorded for this hypothesis yet.

View on SciDEX ↗