Concerted Action of Metals and Macromolecular Crowding on the Fibrillation of α-Synuclein
Larissa A. Munishkina,
Anthony L. Fink,
Vladimir N. Uversky.
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
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