Nitration inhibits fibrillation of human α-synuclein in vitro by formation of soluble oligomers

The aggregation of alpha-synuclein in dopaminergic neurons is a critical factor in the etiology of Parkinson's disease (PD). Oxidative and nitrative stress is also implicated in PD. We examined the effect of nitration on the propensity of alpha-synuclein to fibrillate in vitro. Fibril formation of a-synuclein was completely inhibited by nitration, due to the formation of stable soluble oligomers (apparently octamers). More importantly the presence of sub-stoichiometric concentrations of nitrated a-synuclein led to inhibition of fibrillation of non-modifled a-synuclein. These observations suggest that nitration of soluble a-synuclein may be a protective factor in PD, rather than a causative one. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.