Negatively charged α-synuclein condensate modulates partitioning of molecules.

ABSTRACT: α-Synuclein (αSyn) aggregation via liquid-liquid phase separation (LLPS) has recently emerged as a crucial mechanism underlying amyloid fibril formation implicated in Parkinson's disease. However, comprehensive investigation of the physicochemical properties of αSyn condensate remains incomplete. Here, we demonstrate that αSyn condensates exhibit a highly negative electrostatic potential, revealed by preferential enrichment of positively charged fluorophores or fluorophore-labeled αSyn. We further demonstrate that αSyn LLPS is regulated by a balance between self-association and electrostatic repulsion, with excess negative charge inhibiting phase separation. To study αSyn LLPS in a cellular context, we generated a stably transfected SH-SY5Y cell line that forms gel-like, nontoxic αSyn cond

SUBMITTER: Yang Q 

PROVIDER: S-EPMC12446775 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature