ArticleNeuron2015
ALS/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule Function.
Article in Neuron, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 522 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
522 citing papers in PubMed, 1 synthesis or guideline pooled it, 906 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Biomolecular coacervation-mediated materials: Phase states, phase transitions, and biomedical applications.Bioactive materials · 2027Review
- Probing biomolecular condensates with a minimally perturbative experimental readout framework.The Biochemical journal · 2026Review
- From optical control to translational readiness: an evidence-tiered framework for optogenetics in neuromuscular and neurological disorders.Materials today. Bio · 2026Review
- Fyn kinase: a key mechanistic regulator and therapeutic target in tauopathy and neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Mapping high resolution, multidimensional phase diagrams of near-physiological protein condensates.Nature communications · 2026Article
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Valosin-containing protein counteracts ATP-driven dissolution of FUS condensates through its ATPase activity in vitro.FEBS letters · 2026Article
- Optogenetic Evidence for the Intrinsic Phase Separation Propensity of the Sgs1 N-Terminal Region: Implications for Assemblysome Formation.Biomolecules · 2026Article
- α-Synuclein Forms Distinct Micelle-Like Assemblies at Low Ionic Strengths.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Structural Control of Dual Emission in Coumarin Fluorophores for Visualizing Protein Droplet Maturation.Angewandte Chemie (International ed. in English) · 2026Article
- Advances in the nanostructure characterization of biological hydrogels formed by the prion-like domain of EARLY FLOWERING 3.Acta crystallographica. Section D, Structural biology · 2026Article
- Article
- Nuclear condensates formed by truncated mutant NEK1s impede ribosomal RNA biogenesis and drive motor dysfunction.Nature communications · 2026Article
- Biomolecular condensates mediate C-N bond formation.Nature chemical biology · 2026Article
- Interplay of Noncovalent Interactions in Phase Separation Mediated by Tyrosine-Rich and Arginine-Rich Polypeptides.Journal of the American Chemical Society · 2026Article
- RNA G-quadruplexes function as a tunable switch of FUS phase separation.Nucleic acids research · 2026Article
- Proteomic profile of hippocampal growth cones through early postnatal development.Development (Cambridge, England) · 2026Article
- RNArchitects: how hnRNPs shape neuronal landscapes.Brain : a journal of neurology · 2026Review
- Biomolecular condensates provide a unique environment for redox-mediated protein crosslinking.bioRxiv : the preprint server for biology · 2026Article
462 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 6 institutions in 4 countries.
Funding
Abstract
The mechanisms by which mutations in FUS and other RNA binding proteins cause ALS and FTD remain controversial. We propose a model in which low-complexity (LC) domains of FUS drive its physiologically reversible assembly into membrane-free, liquid droplet and hydrogel-like structures. ALS/FTD mutations in LC or non-LC domains induce further phase transition into poorly soluble fibrillar hydrogels distinct from conventional amyloids. These assemblies are necessary and sufficient for neurotoxicity in a C. elegans model of FUS-dependent neurodegeneration. They trap other ribonucleoprotein (RNP) granule components and disrupt RNP granule function. One consequence is impairment of new protein synthesis by cytoplasmic RNP granules in axon terminals, where RNP granules regulate local RNA metabolism and translation. Nuclear FUS granules may be similarly affected. Inhibiting formation of these fibrillar hydrogel assemblies mitigates neurotoxicity and suggests a potential therapeutic strategy that may also be applicable to ALS/FTD associated with mutations in other RNA binding proteins.
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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.