Nitration Inhibits Fibrillation of Human Alpha-synuclein in Vitro by Formation of Soluble Oligomers

Overview

Journal FEBS Lett

Specialty Biochemistry

Date 2003 May 6

PMID 12729915

Citations 61

Authors

Ghiam Yamin

Vladimir N Uversky

Anthony L Fink

Affiliations

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Abstract

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 alpha-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 alpha-synuclein led to inhibition of fibrillation of non-modified alpha-synuclein. These observations suggest that nitration of soluble alpha-synuclein may be a protective factor in PD, rather than a causative one.

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