Nitration inhibits fibrillation of human alpha-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 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.
Yamin
Ghiam
G
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
Uversky
Vladimir N
VN
Fink
Anthony L
AL
D006801:Humans; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure*; D010300:Parkinson Disease / Q000209:etiology; D012995:Solubility; D051843:Synucleins; D013774:Tetranitromethane / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D014443:Tyrosine; D013774:Tetranitromethane