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, V. N. Uversky.

Journal Name: Current Alzheimer Research

Volume 6 , Issue 3 , 2009

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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

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Article Details

VOLUME: 6
ISSUE: 3
Year: 2009
Page: [252 - 260]
Pages: 9
DOI: 10.2174/156720509788486491
Price: $58

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