ArticleBiomolecules2021
Liquid-Liquid Phase Separation Enhances TDP-43 LCD Aggregation but Delays Seeded Aggregation.
Article in Biomolecules, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 50 citations in OpenAlex.
- CPEB3 selectively inhibits α-synuclein aggregation without modulating TDP-43 pathology.FEBS letters · 2026Article
- Kinetics and Spatial Distribution of β-Sheet Development in TDP-43ACS chemical neuroscience · 2026Article
- An ALS-associated mutation in the C-terminal α-helix of TDP-43 uncouples condensate formation and amyloid assembly.Protein science : a publication of the Protein Society · 2026Article
- [Mechanisms of RNA-binding protein phase separation in steroid-associated necrosis of the femoral head].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Amyloid-β, Tau Protein, α-Synuclein, TDP-43, and FUS in Mixed Pathology: And Intrinsic Disorder to Rule Them All.International journal of molecular sciences · 2026Review
- Small heat shock proteins HspB1 and HspB5 differentially alter the condensation and aggregation of the TDP-43 low-complexity domain.Protein science : a publication of the Protein Society · 2026Article
- Direct observation and quantification of single nanocondensates of the low complexity domain of TDP-43.Nature communications · 2026Article
- Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation.Genome biology · 2026Review
- Enhancer RNA-mediated transcriptional regulation of TDP-43 during early neural lineage specification.Animal cells and systems · 2026Article
- In-Depth Study of Low-Complexity Domains: From Structural Diversity to Disease Mechanisms.Cells · 2025Review
- Repulsive vs Attractive Crowding Distinctly Regulate TDP-43 Condensates through Region-specific Structural Dynamics.JACS Au · 2025Article
- Emergence of Compact Oligomers inside the Small-World Network of TDP-43 Condensates.The journal of physical chemistry letters · 2025Article
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
- Genetic Basis of Motor Neuron Diseases: Insights, Clinical Management, and Future Directions.International journal of molecular sciences · 2025Review
- Molecular mechanisms and consequences of TDP-43 phosphorylation in neurodegeneration.Molecular neurodegeneration · 2025Review
- Cross-Interaction with Amyloid-β Drives Pathogenic Structural Transformation within the Amyloidogenic Core Region of TDP-43.ACS chemical neuroscience · 2025Article
- The Regulation of TDP-43 Structure and Phase Transitions: A Review.The protein journal · 2025Review
- Hydrogen-Deuterium Exchange Mass Spectrometry Reveals Mechanistic Insights into RNA Oligonucleotide-Mediated Inhibition of TDP-43 Aggregation.Journal of the American Chemical Society · 2024Article
- Uncovering Intermolecular Interactions Driving the Liquid-Liquid Phase Separation of the TDP-43 Low-Complexity Domain via Atomistic Dimerization Simulations.Journal of chemical information and modeling · 2024Article
- Cellular Prion Protein Conformational Shift after Liquid-Liquid Phase Separation Regulated by a Polymeric Antagonist and Mutations.Journal of the American Chemical Society · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Aggregates of TAR DNA-binding protein (TDP-43) are a hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Although TDP-43 aggregates are an undisputed pathological species at the end stage of these diseases, the molecular changes underlying the initiation of aggregation are not fully understood. The aim of this study was to investigate how phase separation affects self-aggregation and aggregation seeded by pre-formed aggregates of either the low-complexity domain (LCD) or its short aggregation-promoting regions (APRs). By systematically varying the physicochemical conditions, we observed that liquid-liquid phase separation (LLPS) promotes spontaneous aggregation. However, we noticed less efficient seeded aggregation in phase separating conditions. By analyzing a broad range of conditions using the Hofmeister series of buffers, we confirmed that stabilizing hydrophobic interactions prevail over destabilizing electrostatic forces. RNA affected the cooperativity between LLPS and aggregation in a "reentrant" fashion, having the strongest positive effect at intermediate concentrations. Altogether, we conclude that conditions which favor LLPS enhance the subsequent aggregation of the TDP-43 LCD with complex dependence, but also negatively affect seeding kinetics.
Indexed as
Identifiers
What OpenQuestion holds
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.