Abstract

Alpha-synuclein (AS) is a presynaptic protein lacking a unique secondary structure in solution. AS amyloid aggregates in dopaminergic neurons are the hallmark of Parkinson's disease (PD). The aggregation involves structural transitions from monomeric AS to oligomeric presumably neurotoxic and fibril formation. In spite of its importance for the understanding PD pathobiology and devising rational, targeted therapeutic strategies, details on the aggregation process remain largely unknown. Methodologies and reagents capable of controlling aggregation kinetics are essential tools for the investigation of the molecular amyloid mechanisms. In this work we investigated the influence of citrate capped gold nanoparticles on the aggregation kinetics of AS using a fluorescent probe (MFC) sensitive to the polarity of the molecular microenvironment via an excited state intramolecular proton transfer (ESIPT). The particular effects on the half time, nucleation time and growth rate were ascertained. Gold nanoparticles produced a strong acceleration, with an influence on the nucleation and growth phases of the mechanism. The effects were dependent on the size and concentration of the nanoparticles, being strongest for nanoparticles 10 nm in diameter, with a 3-fold increase in the overall aggregation rate at low concentrations as 20 nM.

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