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 alpha-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 alpha-synuclein fibrillation in the presence of high concentrations of polyethylene glycol. This suggests that the fibril-promoting effects of factors inducing partial folding of alpha-synuclein and the fibril-stimulating effects of macromolecular crowding are relatively independent and thus might act additively or even synergistically.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anions / pharmacology
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Chemical Phenomena
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Dose-Response Relationship, Drug
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Drug Interactions
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Escherichia coli
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Glycosaminoglycans / pharmacology
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Hydrogen-Ion Concentration
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Macromolecular Substances / metabolism*
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Metals / pharmacology
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Methylamines / pharmacology
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Microscopy, Electron
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Models, Molecular
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Oxidants / pharmacology
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Polyethylene Glycols / pharmacology
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Protein Binding / drug effects
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Static Electricity
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Time Factors
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alpha-Synuclein / chemistry*
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alpha-Synuclein / metabolism*
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alpha-Synuclein / ultrastructure
Substances
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Anions
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Glycosaminoglycans
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Macromolecular Substances
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Metals
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Methylamines
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Oxidants
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alpha-Synuclein
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Polyethylene Glycols
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trimethyloxamine