Local Ionic Conditions Modulate the Aggregation Propensity and Influence the Structural Polymorphism of α-Synuclein.

ABSTRACT: Parkinson's disease (PD) is linked to the aggregation of the intrinsically disordered protein α-synuclein (aSyn), but the precise triggers and mechanisms driving this process remain unclear. Local environmental factors, such as ion concentrations, can influence aSyn's conformational ensemble and its tendency to aggregate. In this study, we explore how physiologically relevant ions, mainly Ca²⁺ and Na⁺, affect aSyn aggregation, monomer structural dynamics, and fibril polymorphism. ThT fluorescence assays show that all ions speed up aggregation, with Ca²⁺ having the strongest effect. Using heteronuclear single quantum correlation nuclear magnetic resonance (¹H-¹⁵N HSQC NMR) spectroscopy, we validate that Ca²⁺ binds at the C-te

SUBMITTER: Zacharopoulou M 

PROVIDER: S-EPMC12023029 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature