The Effect of Macromolecular Crowding on Protein Aggregation and Amyloid Fibril Formation
Document Type
Article
Publication Date
2004
Digital Object Identifier (DOI)
https://doi.org/10.1002/jmr.699
Abstract
Macromolecular crowding is expected to have several significant effects on protein aggregation; the major effects will be those due to excluded volume and increased viscosity. In this report we summarize data demonstrating that macromolecular crowding may lead to a dramatic acceleration in the rate of protein aggregation and formation of amyloid fibrils, using the protein α-synuclein. The aggregation of α-synuclein has been implicated as a critical factor in development of Parkinson's disease. Various types of polymers, from neutral polyethylene glycols and polysaccharides (Ficolls, dextrans) to inert proteins, are shown to accelerate α-synuclein fibrillation. The stimulation of fibrillation increases with increasing length of polymer, as well as increasing polymer concentration. At lower polymer concentrations (typically up to ∼100 mg/ml) the major effect is ascribed to excluded volume, whereas at higher polymer concentrations evidence of opposing viscosity effects become apparent. Pesticides and metals, which are linked to increased risk of Parkinson's disease by epidemiological studies, are shown to accelerate α-synuclein fibrillation under conditions of molecular crowding. Copyright © 2004 John Wiley & Sons, Ltd.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Journal of Molecular Recognition, v. 17, issue 5, p. 456-464
Scholar Commons Citation
Munishkina, Larissa A.; Cooper, Elisa M.; Uversky, Vladimir N.; and Fink, Anthony L., "The Effect of Macromolecular Crowding on Protein Aggregation and Amyloid Fibril Formation" (2004). Molecular Medicine Faculty Publications. 728.
https://digitalcommons.usf.edu/mme_facpub/728
