Concerted action of metals and macromolecular crowding on the fibrillation of alpha-synuclein.
Certain metals lead to increased risk of Parkinson's disease (PD) and the aggregation of alpha-synuclein is implicated in the PD pathology. Although alpha-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 alpha-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.
Munishkina
Larissa A
LA
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
Fink
Anthony L
AL
Uversky
Vladimir N
VN
D000818:Animals; D002417:Cattle; D006801:Humans; D008670:Metals / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism*
D008670:Metals; D051844:alpha-Synuclein