ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Phase Separation and Aggregation of α-Synuclein Diverge at Different Salt Conditions.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Article
- Strategic physicochemical tuning: amphiphilic polymers as molecular regulators of amyloid aggregation and cytotoxicity.Chemical science · 2026Article
- CPEB3 selectively inhibits α-synuclein aggregation without modulating TDP-43 pathology.FEBS letters · 2026Article
- Nanopipettes Enable Native Mass Spectrometry Studies of the Intrinsically Disordered Protein α-Synuclein in Biochemical Buffers.Analytical chemistry · 2026Article
- In Search of Shape in the Unshaped: Constructing Ensembles of Intrinsically Disordered Proteins.Biophysics reviews · 2026Article
- Time-Resolved SAXS Reveals Distinct Millisecond Metal-Induced Conformational Dynamics of Monomeric α-Synuclein.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
- 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
- Residue-Specific Modulation of Aggregation-Associated Interactions by Spermine in Tau, α‑Synuclein, and Aβ40.JACS Au · 2026Article
- Alzheimer's Aβ catalyzes Tau phase separation and aggregation via early nanocluster solubilization.Nature communications · 2026Article
- A global thermodynamic-kinetic model capturing the hallmarks of liquid-liquid phase separation and amyloid aggregation.Cell reports. Physical science · 2026Article
- From dynamic condensates to pathological assemblies: the phase behavior of tau andFrontiers in molecular neuroscience · 2026Review
- Residue-Specific Modulation of Aggregation-Associated Interactions by Spermine in Tau, α-Synuclein, and Aβ40.bioRxiv : the preprint server for biology · 2025Article
- APOE Genotype Difference in the Biphasic Modulation of Amyloid-β Aggregation by Direct Binding and Lowering the Nucleation Barrier.Biomacromolecules · 2025Article
- Spermine modulation of Alzheimer's Tau and Parkinson's α-synuclein: implications for biomolecular condensation and neurodegeneration.Nature communications · 2025Article
- Molecular mechanisms mediated by liquid-liquid phase separation in chronic liver disease progression.iScience · 2025Review
- Dissecting the Molecular Determinants of α-synuclein Phase Separation and Condensate Aging: The Pivotal Role of β-Sheet-Rich Motifs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Theoretical Methods for Assessing the Density of Protein Nanodroplets.International journal of molecular sciences · 2025Article
- Biomolecular Condensates as Emerging Biomaterials: Functional Mechanisms and Advances in Computational and Experimental Approaches.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- Structural and Functional Relevance of Charge-Based Transient Interactions inside Intrinsically Disordered Proteins.ACS physical chemistry Au · 2025Article
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Abstract
The coacervation of alpha-synuclein (αSyn) into cytotoxic oligomers and amyloid fibrils are considered pathological hallmarks of Parkinson's disease. While aggregation is central to amyloid diseases, liquid-liquid phase separation (LLPS) and its interplay with aggregation have gained increasing interest. Previous work shows that factors promoting or inhibiting aggregation have similar effects on LLPS. This study provides a detailed scanning of a wide range of parameters, including protein, salt and crowding concentrations at multiple pH values, revealing different salt dependencies of aggregation and LLPS. The influence of salt on aggregation under crowding conditions follows a non-monotonic pattern, showing increased effects at medium salt concentrations. This behavior can be elucidated through a combination of electrostatic screening and salting-out effects on the intramolecular interactions between the N-terminal and C-terminal regions of αSyn. By contrast, this study finds a monotonic salt dependence of LLPS due to intermolecular interactions. Furthermore, it observes time evolution of the two distinct assembly states, with macroscopic fibrillar-like bundles initially forming at medium salt concentration but subsequently converting into droplets after prolonged incubation. The droplet state is therefore capable of inhibiting aggregation or even dissolving aggregates through heterotypic interactions, thus preventing αSyn from its dynamically arrested state.
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