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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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

Author(s): L. A. Munishkina, A. L. Fink and V. N. Uversky

Volume 6, Issue 3, 2009

Page: [252 - 260] Pages: 9

DOI: 10.2174/156720509788486491

Price: $65


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

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