Modulation of biomolecular condensation of alpha-synuclein variants by eprodisate

Abstract

Aggregation of α-synuclein (α-SYN) into amyloid structures is closely associated with Parkinson’s disease (PD). Prevention of α-SYN aggregation has been validated as a key strategy to manage PD. α-SYN undergoes liquid-liquid phase separation (LLPS) via biomolecular condensation that facilitates nucleation and amyloid formation in liquid droplets. In this work, the effect of eprodisate (a glycosaminoglycan mimetic) on the formation of biomolecular condensates by α-SYN and its pathology-relevant variants has been investigated. Eprodisate affected the formation of α-SYN condensates, increased the fluidity inside droplets and inhibited α-SYN from turning into amyloid. It also attenuated aggregation of α-SYN variants in the presence of chondroitin sulphate. Eprodisate inhibited phase separation, hydrogel formation and amyloid aggregation of PD-related α-SYN A30P, α-SYN S129D and C-terminal truncated variants. It reduced oxidative stress, decreased α-SYN-positive aggregates and increased cell survival. These findings show that eprodisate may be explored further as an ameliorative therapy in PD.

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Item Type:	Article
Authors/Creators:	Biswas, S. Mavlankar, N.A. Panuganti, V. Pal, A. Roy, I. https://orcid.org/0000-0001-5602-1714
Copyright, Publisher and Additional Information:	© The Author(s) 2026. Open Access: This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Keywords:	Biophysical chemistry; Protein aggregation; Proteins
Dates:	Accepted: 9 April 2026 Published (online): 27 April 2026 Published: 2 July 2026
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Engineering (Sheffield) > School of Chemical, Materials and Biological Engineering
Date Deposited:	22 Jul 2026 15:42
Last Modified:	22 Jul 2026 15:42
Status:	Published
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	10.1038/s42004-026-02032-4
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:243711

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Modulation of biomolecular condensation of alpha-synuclein variants by eprodisate

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