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Updated: Aug 12, 2026

Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo
Published on: June 2, 2019
Methionine oxidation inhibits fibrillation of human alpha-synuclein in vitro
Vladimir N Uversky1, Ghiam Yamin, Pierre O Souillac
1Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA. uversky@hydrogen.ucsc.edu
Abstract:
We examined the effect of methionine oxidation of human recombinant alpha-synuclein on its structural properties and propensity to fibrillate. Both oxidized and non-oxidized alpha-synucleins were natively unfolded under conditions of neutral pH, with the oxidized protein being slightly more disordered. Both proteins adopted identical partially folded conformations under conditions of acidic pH. The fibrillation of alpha-synuclein at neutral pH was completely inhibited by methionine oxidation. This inhibitory effect was eliminated at low pH. The addition of oxidized alpha-synuclein to the unoxidized form led to a substantial inhibition of alpha-synuclein fibrillation.

