ArticleCell2025
Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates.
Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed.
- AI-Powered, Temperature-Resolved Centrifugal Microfluidics for Rapid 3D Phase-Diagram Generation of Biomolecular Condensates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- α-Synuclein Forms Distinct Micelle-Like Assemblies at Low Ionic Strengths.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Biomolecular condensates as dynamic regulators of musculoskeletal homeostasis, disease, and therapeutic challenges.Bone research · 2026Review
- BOULE is Essential for the Dynamic Disassembly of Heat Shock Granules in Male Germ Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inhibition and Formation of Amyloid Fibrils in the Bulk and at the Interface of Biomolecular Condensates.Angewandte Chemie (International ed. in English) · 2026Review
- A practical guide to investigating biomolecular condensates: a comment from the plant community.Science China. Life sciences · 2026Review
- Fine-Tuned Regulation of mRNA Translation and Transport by STAU2 Condensate Facilitates Neuronal Development and Plasticity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protein thiol alterations drive pathologic liquid-liquid phase separation in the aging brain.Nature structural & molecular biology · 2026Article
- The emerging synergy of experimental and computational approaches for therapeutic modulation of biomolecular condensates.SLAS discovery : advancing life sciences R & D · 2026Review
- Lipid droplets promote aberrant liquid-liquid phase separation of alpha-synuclein impairing energy homeostasis.EMBO reports · 2026Article
- Condensation of MATCAP promotes CENP-E-dependent chromosome congression in mitosis.Nature communications · 2026Article
- Targeting astrocyte-mediated neurotoxicity induced by ALS/FTD-associated RNA binding proteins.Cell communication and signaling : CCS · 2026Article
- Proteome-scale quantification of the interactions driving condensate formation of intrinsically disordered proteins.Nature communications · 2026Article
- Article
- Hierarchical Nuclear Architecture in Pre-mRNA Splicing: From IDRs to Speckles and Meshworks.International journal of molecular sciences · 2026Review
- Orthogonal Ionic Liquid-Based Extraction Strategy Enables Amyloid-Specific Profiling of Aggregate Proteome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protein Disulfide Isomerase Disassembles TDP-43/G3BP1 Condensates and Antagonizes TDP-43 Pathological Aggregates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Biomolecular condensates mediate C-N bond formation.Nature chemical biology · 2026Article
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Concentration-dependent cytoplasmic phase separation of TDP-43 drives aggregation and proteinopathy.The FEBS journal · 2026Article
36 more citing papers are in PubMed but not listed here.
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25 authors.
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Abstract
Cytosolic aggregation of the nuclear protein TAR DNA-binding protein 43 (TDP-43) is associated with many neurodegenerative diseases, but the triggers for TDP-43 aggregation are still debated. Here, we demonstrate that TDP-43 aggregation requires a double event. One is up-concentration in stress granules beyond a threshold, and the other is oxidative stress. These two events collectively induce intra-condensate demixing, giving rise to a dynamic TDP-43-enriched phase within stress granules, which subsequently transition into pathological aggregates. Intra-condensate demixing of TDP-43 is observed in iPS-motor neurons, a disease mouse model, and patient samples. Mechanistically, intra-condensate demixing is triggered by local unfolding of the RRM1 domain for intermolecular disulfide bond formation and by increased hydrophobic patch interactions in the C-terminal domain. By engineering TDP-43 variants resistant to intra-condensate demixing, we successfully eliminate pathological TDP-43 aggregates in cells. We suggest that up-concentration inside condensates followed by intra-condensate demixing could be a general pathway for protein aggregation.
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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.