Abstract
Certain metals lead to increased risk of Parkinsons disease (PD) and the aggregation of α-synuclein is implicated in the PD pathology. Although α-synuclein fibrillation has been extensively studied in dilute solutions in vitro, the intracellular environment is highly crowded. We are showing here that certain metals cause a significant acceleration of α-synuclein fibrillation in the presence of high concentrations of various macromolecules mostly through decreasing the fibrillation lagtime. The faster fibrillation in crowded environments in the presence of heavy metals suggests a simple molecular basis for the observed elevated risk of PD due to exposure to metals.
Keywords: Parkinson's disease, α-synuclein, crowding, fibrillation, aggregation, metals
Protein & Peptide Letters
Title: Concerted Action of Metals and Macromolecular Crowding on the Fibrillation of α-Synuclein
Volume: 15 Issue: 10
Author(s): Larissa A. Munishkina, Anthony L. Fink and Vladimir N. Uversky
Affiliation:
Keywords: Parkinson's disease, α-synuclein, crowding, fibrillation, aggregation, metals
Abstract: Certain metals lead to increased risk of Parkinsons disease (PD) and the aggregation of α-synuclein is implicated in the PD pathology. Although α-synuclein fibrillation has been extensively studied in dilute solutions in vitro, the intracellular environment is highly crowded. We are showing here that certain metals cause a significant acceleration of α-synuclein fibrillation in the presence of high concentrations of various macromolecules mostly through decreasing the fibrillation lagtime. The faster fibrillation in crowded environments in the presence of heavy metals suggests a simple molecular basis for the observed elevated risk of PD due to exposure to metals.
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Cite this article as:
Munishkina A. Larissa, Fink L. Anthony and Uversky N. Vladimir, Concerted Action of Metals and Macromolecular Crowding on the Fibrillation of α-Synuclein, Protein & Peptide Letters 2008; 15 (10) . https://dx.doi.org/10.2174/092986608786071102
DOI https://dx.doi.org/10.2174/092986608786071102 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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