Aggregation of alpha-Synuclein Induced by Oxidized Catecholamines as a Potential Mechanism of Lewy Body

摘要

Lewy bodies (LBs) are neuronal inclusions that are closely related to Parkinson's disease (PD).The filamentous component of LB from patients with PD contains biochemically altered alpha-synuclein.We have investigated the effect of the oxidized products of catecholamines on the modification of alpha-synuclein.When alpha-synuclein was incubated with the oxidized 3,4-dihydroxyphenylalanine (L-DOPA) or dopamine,the protein was induced to be aggregated.The oxidized catecholamine-mediated alpha-synuclein aggregation was enhanced by copper ion.Radical scavengers,azide and N-acetyl cysteine significantly prevented the oxidized catecholamine-mediated alpha-synuclein aggregation.The results suggest that free radical may play a role in alpha-synuclein aggregation.Exposure of alpha-synuclein to the oxidized products of catecholamines led to the formation of dityrosine.Antioxidant dipeptides carnosine,homocarnosine and anserine significantly protected alpha-synuclein from the aggregation induced by the oxidized products of catecholamines.