ArticleThe Journal of biological chemistry2019
The role of liquid-liquid phase separation in aggregation of the TDP-43 low-complexity domain.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 226 papers.
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Who cites it
226 citing papers in PubMed, 401 citations in OpenAlex.
- Computational design of metalloproteases.Nature · 2026Article
- Unraveling in vitro phase separation and aggregation properties of the structured region of FMRP and the impact of Fragile X syndrome-linked mutations.The FEBS journal · 2026Article
- Article
- Phase separation in neurodegenerative disorders: a metabolic perspective on protein aggregation and therapeutic targeting.Translational neurodegeneration · 2026Review
- Article
- Deletion Analysis of Phase Separation, Amyloid Formation and Prion Propagation by the Intrinsically Disordered Region of Yeast Sup35 Protein.International journal of molecular sciences · 2026Article
- α-Synuclein Forms Distinct Micelle-Like Assemblies at Low Ionic Strengths.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protease-Mediated TAR DNA-Binding Protein 43 (TDP-43) Pathogenesis: From Molecular Mechanisms to Therapeutic Opportunities.ACS pharmacology & translational science · 2026Review
- Inhibition and Formation of Amyloid Fibrils in the Bulk and at the Interface of Biomolecular Condensates.Angewandte Chemie (International ed. in English) · 2026Review
- Unravelling the Significance of Cystatin C and Bunina Bodies in Amyotrophic Lateral Sclerosis Pathogenesis.Neuropathology and applied neurobiology · 2026Review
- Article
- Annexin A11 and TDP-43: core players in neurodegeneration.Acta neuropathologica · 2026Review
- AI-discovered protein fragments as generalizable regulators of biomolecular condensates.bioRxiv : the preprint server for biology · 2026Article
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- CPEB3 selectively inhibits α-synuclein aggregation without modulating TDP-43 pathology.FEBS letters · 2026Article
- Divergent effects of pathological α-synuclein truncations and mutations on phase separation.Nature communications · 2026Article
- Size of Biomolecular Condensates Dictates Fate in Liquid-Solid Phase Transitions through Amorphous-Amyloid Competition.Journal of the American Chemical Society · 2026Article
- Site-Specific Raman Probes Reveal Droplet Aging and Residue-Level Fibril Polymorphism in TDP-43Journal of the American Chemical Society · 2026Article
- Kinetics and Spatial Distribution of β-Sheet Development in TDP-43ACS chemical neuroscience · 2026Article
- Small heat shock protein HSPB8 interacts with a pre-fibrillar TDP43 low complexity domain species to delay fibril formation.Biophysical chemistry · 2026Article
166 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Pathological aggregation of the transactive response DNA-binding protein of 43 kDa (TDP-43) is associated with several neurodegenerative disorders, including ALS, frontotemporal dementia, chronic traumatic encephalopathy, and Alzheimer's disease. TDP-43 aggregation appears to be largely driven by its low-complexity domain (LCD), which also has a high propensity to undergo liquid-liquid phase separation (LLPS). However, the mechanism of TDP-43 LCD pathological aggregation and, most importantly, the relationship between the aggregation process and LLPS remains largely unknown. Here, we show that amyloid formation by the LCD is controlled by electrostatic repulsion. We also demonstrate that the liquid droplet environment strongly accelerates LCD fibrillation and that its aggregation under LLPS conditions involves several distinct events, culminating in rapid assembly of fibrillar aggregates that emanate from within mature liquid droplets. These combined results strongly suggest that LLPS may play a major role in pathological TDP-43 aggregation, contributing to pathogenesis in neurodegenerative diseases.
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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.