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

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Gags, Parkinson's Disease, Aggregation, Crowding, Fibrillation, Metals, Organic Solvent, Pesticides, Polycations, α-synuclein

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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.

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Current Alzheimer Research, v. 6, issue 3, p. 252-260