ArticleNature chemistry2020
α-Synuclein aggregation nucleates through liquid-liquid phase separation.
Article in Nature chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 429 papers.
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Who cites it
429 citing papers in PubMed, 858 citations in OpenAlex.
- Biomolecular coacervation-mediated materials: Phase states, phase transitions, and biomedical applications.Bioactive materials · 2027Review
- Protein-Independent Liquid-Liquid Phase Separation of Adenosine Triphosphate Under Crowded Conditions.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Decoding Biomolecular Phase Separation: From Physiological Roles to Pathological Mechanisms and Therapeutic Biomaterials Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Excess Met1-linked ubiquitination leads to solid aggregate formation.The EMBO journal · 2026Article
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- 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
- Zinc Fingers as Programmable Metalloprotein Scaffolds for Altering Pathogenic Biomolecular Phase Transitions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Solvent-Mediated Phase Propagation Governs Excitonic Heterogeneity in Chiral Fibrils.ACS central science · 2026Article
- Biomolecular Condensates Integrate Transcriptional and Epigenetic Responses to Hypoxia.International journal of molecular sciences · 2026Review
- Dual effect of α-synuclein disease variants on condensate formation.Nature communications · 2026Article
- Aberrant phase separation from a rare ABI3 mutation drives microglial dysfunction and Alzheimer's risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Phase separation in neurodegenerative disorders: a metabolic perspective on protein aggregation and therapeutic targeting.Translational neurodegeneration · 2026Review
- G3BP1 depletion, observed in Parkinson's Disease, drives Golgi-lysosome-autophagy defects.Cell death and differentiation · 2026Article
- 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
- Structural Control of Dual Emission in Coumarin Fluorophores for Visualizing Protein Droplet Maturation.Angewandte Chemie (International ed. in English) · 2026Article
- Review
- 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
- Lipid droplets promote aberrant liquid-liquid phase separation of alpha-synuclein impairing energy homeostasis.EMBO reports · 2026Article
369 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
α-Synuclein (α-Syn) aggregation and amyloid formation is directly linked with Parkinson's disease pathogenesis. However, the early events involved in this process remain unclear. Here, using the in vitro reconstitution and cellular model, we show that liquid-liquid phase separation of α-Syn precedes its aggregation. In particular, in vitro generated α-Syn liquid-like droplets eventually undergo a liquid-to-solid transition and form an amyloid hydrogel that contains oligomers and fibrillar species. Factors known to aggravate α-Syn aggregation, such as low pH, phosphomimetic substitution and familial Parkinson's disease mutations, also promote α-Syn liquid-liquid phase separation and its subsequent maturation. We further demonstrate α-Syn liquid-droplet formation in cells. These cellular α-Syn droplets eventually transform into perinuclear aggresomes, the process regulated by microtubules. This work provides detailed insights into the phase-separation behaviour of natively unstructured α-Syn and its conversion to a disease-associated aggregated state, which is highly relevant in Parkinson's disease pathogenesis.
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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.