Concerted Action of Metals and Macromolecular Crowding on the Fibrillation of α-Synuclein
Larissa A. Munishkina, Anthony L. Fink and Vladimir N. Uversky
Pages 1079-1085 (7)
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.
Parkinson's disease, α-synuclein, crowding, fibrillation, aggregation, metals
Department of Biochemistry and Molecular Biology, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 410 W. 10th Street, HS 5009, Indianapolis, IN 46202-2111, USA.