title: Accelerated fibrillation of alpha-synuclein induced by the combined action of macromolecular crowding and factors inducing partial folding.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Munishkina
authors.forename: A L
authors.initials: AL
authors.lastname: Fink
authors.forename: V N
authors.initials: VN
authors.lastname: Uversky
mesh_terms: D000818:Animals; D000838:Anions / Q000494:pharmacology; D055598:Chemical Phenomena; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004926:Escherichia coli; D006025:Glycosaminoglycans / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D046911:Macromolecular Substances / Q000378:metabolism*; D008670:Metals / Q000494:pharmacology; D008744:Methylamines / Q000494:pharmacology; D008854:Microscopy, Electron; D008958:Models, Molecular; D016877:Oxidants / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D055672:Static Electricity; D013997:Time Factors; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000838:Anions; D006025:Glycosaminoglycans; D046911:Macromolecular Substances; D008670:Metals; D008744:Methylamines; D016877:Oxidants; D051844:alpha-Synuclein; D011092:Polyethylene Glycols; C005855:trimethyloxamine