期刊
JOURNAL OF MOLECULAR RECOGNITION
卷 17, 期 5, 页码 456-464出版社
WILEY
DOI: 10.1002/jmr.699
关键词
alpha-synuclein; amyloid fibril; polyethylene glycol; Ficoll; dextran; crowding agent; conformational change; partially folded intermediate
资金
- NINDS NIH HHS [NS39985] Funding Source: Medline
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 a-synuclein. The aggregation of a-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 a-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 similar to100mg/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 alpha-synuclein fibrillation under conditions of molecular crowding. Copyright (C) 2004 John Wiley Sons, Ltd.
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