Accelerated fibrillation of alpha-synuclein induced by the combined action of macromolecular crowding and factors inducing partial folding

Curr Alzheimer Res. 2009 Jun;6(3):252-60. doi: 10.2174/156720509788486491.


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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anions / pharmacology
  • Chemical Phenomena
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Escherichia coli
  • Glycosaminoglycans / pharmacology
  • Hydrogen-Ion Concentration
  • Macromolecular Substances / metabolism*
  • Metals / pharmacology
  • Methylamines / pharmacology
  • Microscopy, Electron
  • Models, Molecular
  • Oxidants / pharmacology
  • Polyethylene Glycols / pharmacology
  • Protein Binding / drug effects
  • Static Electricity
  • Time Factors
  • alpha-Synuclein / chemistry*
  • alpha-Synuclein / metabolism*
  • alpha-Synuclein / ultrastructure


  • Anions
  • Glycosaminoglycans
  • Macromolecular Substances
  • Metals
  • Methylamines
  • Oxidants
  • alpha-Synuclein
  • Polyethylene Glycols
  • trimethyloxamine