Accelerated Fibrillation of α-Synuclein Induced by the Combined Action of Macromolecular Crowding and Factors Inducing Partial Folding

L.   A.   Munishkina; A.   L.   Fink; V.   N.   Uversky

Abstract

To better model the characteristics of crowded intracellular environments, we examined the effect of several factors known to induce partial folding and accelerated fibrillation of α-synuclein in dilute solutions, on the fibrillation of this protein in a crowded milieu. We found that low pH, certain metals and pesticides, polyanions, polycations and low concentrations of organic solvents cause a significant acceleration of α-synuclein fibrillation in the presence of high concentrations of polyethylene glycol. This suggests that the fibril-promoting effects of factors inducing partial folding of α- synuclein and the fibril-stimulating effects of macromolecular crowding are relatively independent and thus might act additively or even synergistically.

Keywords: Parkinson's disease, -synuclein, crowding, fibrillation, aggregation, metals, pesticides, organic solvent, polycations, GAGs