Evidence map›Paper›PMID 38973194›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

Phase Separation and Aggregation of α-Synuclein Diverge at Different Salt Conditions.

Rebecca Sternke-Hoffmann, Xun Sun, Andreas Menzel, Miriam Dos Santos Pinto, Urte Venclovaite, Michael Wördehoff, Wolfgang Hoyer, Wenwei Zheng, Jinghui Luo

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed.

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  18. Theoretical Methods for Assessing the Density of Protein Nanodroplets.International journal of molecular sciences · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Rebecca Sternke-HoffmannCenter for Life Sciences, Paul Scherrer Institute, Forschungsstrasse 111, Villigen, 5232, Switzerland.
Xun SunCenter for Life Sciences, Paul Scherrer Institute, Forschungsstrasse 111, Villigen, 5232, Switzerland.
Andreas MenzelCenter for Photon Science, Paul Scherrer Institute, Forschungsstrasse 111, Villigen, 5232, Switzerland.
Miriam Dos Santos PintoCenter for Life Sciences, Paul Scherrer Institute, Forschungsstrasse 111, Villigen, 5232, Switzerland.
Urte VenclovaiteCenter for Life Sciences, Paul Scherrer Institute, Forschungsstrasse 111, Villigen, 5232, Switzerland.
Michael WördehoffInstitut für Physikalische Biologie, Heinrich-Heine University Düsseldorf, 40225, Düsseldorf, Germany.
Wolfgang HoyerInstitut für Physikalische Biologie, Heinrich-Heine University Düsseldorf, 40225, Düsseldorf, Germany.
Wenwei ZhengCollege of Integrative Sciences and Arts, Arizona State University, Mesa, AZ, 85212, USA.
Jinghui LuoCenter for Life Sciences, Paul Scherrer Institute, Forschungsstrasse 111, Villigen, 5232, Switzerland.ORCID 0000-0002-7014-8153

Funding

Decoding the mechanism of disordered protein interactionsR35GM146814 · NIGMS · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI Wenwei Zheng · 2022 to 2026
$1.8M
BrightFocus Foundation A20201759SNational Science Foundation MCB-2015030NIGMS NIH HHS R35 GM146814NIH HHS R35GM146814Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 197626
6 · The paper itself

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.

Indexed as

alpha-SynucleinProtein AggregatesAmyloidHumansHydrogen-Ion ConcentrationParkinson DiseasePhase SeparationProtein Aggregation, PathologicalSaltsalpha-SynucleinAmyloidProtein AggregatesSaltsaggregationbiomolecular condensatesintrinsically disordered proteinsliquid–liquid phase separationmolecular dynamics

Identifiers

PMID38973194
PMCPMC11425899

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Registered trials

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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.