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
Current Alzheimer Research
Title: Accelerated Fibrillation of α-Synuclein Induced by the Combined Action of Macromolecular Crowding and Factors Inducing Partial Folding
Volume: 6 Issue: 3
Author(s): L. A. Munishkina, A. L. Fink and V. N. Uversky
Affiliation:
Keywords: Parkinson's disease, -synuclein, crowding, fibrillation, aggregation, metals, pesticides, organic solvent, polycations, GAGs
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.
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Cite this article as:
Munishkina A. L., Fink L. A. and Uversky N. V., Accelerated Fibrillation of α-Synuclein Induced by the Combined Action of Macromolecular Crowding and Factors Inducing Partial Folding, Current Alzheimer Research 2009; 6 (3) . https://dx.doi.org/10.2174/156720509788486491
DOI https://dx.doi.org/10.2174/156720509788486491 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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