ArticleMolecular cell2018
Poly(ADP-Ribose) Prevents Pathological Phase Separation of TDP-43 by Promoting Liquid Demixing and Stress Granule Localization.
Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 276 papers.
What it found
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Who cites it
276 citing papers in PubMed, 414 citations in OpenAlex.
- PARylation at the Genome-Proteome Interface: Regulation of DNA Repair Protein Dynamics.International journal of molecular sciences · 2026Review
- Review
- Therapeutic targeting of the conserved region within the low-complexity domain of TDP-43 is neuroprotective and extends survival in amyotrophic lateral sclerosis mice.Nature aging · 2026Article
- TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.Biochemical Society transactions · 2026Review
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- PARylation in Parkinson's disease: a bridge between Lewy body formation and neuronal cell death.Cell death & disease · 2026Article
- TDP-43 oxidation and PP1 crosstalk at RNA granule-mitochondria contact sites.Nature communications · 2026Article
- Embedded CRISPRi Enhances Gene-Silencing Efficiency in Drosophila.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PHKG2 confers resistance of ESCC to cisplatin and enhances CXCL8-dependent immunosuppression to exacerbate tumorigenesis.Cell death & disease · 2026Article
- Maintenance and disruption of the physiological dimer structure of TDP-43 in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.BMC medicine · 2026Review
- Short RNA chaperones promote aggregation-resistant TDP-43 conformers to mitigate neurodegeneration.Science (New York, N.Y.) · 2026Article
- Targeting the NADTrends in molecular medicine · 2026Review
- NADAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Condensate State as Determinant of Amyloid Pathology in Neurodegeneration.Biomolecules · 2026Review
- Poly(ADP-ribose) (PAR) exhibits ion-dependent structural properties distinct from RNA.Nucleic acids research · 2026Article
- Tankyrases and Their Binding Proteins: Origins of Their Roles in Diverse Cellular Pathways.Cells · 2026Review
- Scaffold-client behavior and structural organization in multicomponent protein condensates as revealed by studying tau/TDP-43 droplets.Communications chemistry · 2026Article
- Stress granules as a central hub linking organelle stress, aging, and neurodegeneration.BMB reports · 2026Review
- Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation.Genome biology · 2026Review
- Review
216 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
In amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD), cytoplasmic aggregates of hyperphosphorylated TDP-43 accumulate and colocalize with some stress granule components, but how pathological TDP-43 aggregation is nucleated remains unknown. In Drosophila, we establish that downregulation of tankyrase, a poly(ADP-ribose) (PAR) polymerase, reduces TDP-43 accumulation in the cytoplasm and potently mitigates neurodegeneration. We establish that TDP-43 non-covalently binds to PAR via PAR-binding motifs embedded within its nuclear localization sequence. PAR binding promotes liquid-liquid phase separation of TDP-43 in vitro and is required for TDP-43 accumulation in stress granules in mammalian cells and neurons. Stress granule localization initially protects TDP-43 from disease-associated phosphorylation, but upon long-term stress, stress granules resolve, leaving behind aggregates of phosphorylated TDP-43. Finally, small-molecule inhibition of Tankyrase-1/2 in mammalian cells inhibits formation of cytoplasmic TDP-43 foci without affecting stress granule assembly. Thus, Tankyrase inhibition antagonizes TDP-43-associated pathology and neurodegeneration and could have therapeutic utility for ALS and FTD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.