Abstract
α-Synuclein accumulates in Lewy bodies and two missense mutations, A30P and A53T, have been linked to familial Parkinson's disease. Neither the normal function of α-synuclein nor the pathomechanism of α-synuclein-induced neuropathy are known. SK-N-MC neuroblastoma cells were transiently transfected with either wt α-synuclein, or its mutants, and their abilities to protect against oxidative stress were assessed. At low expression levels (1 μg cDNA/10 5 cells), all three synuclein variants were devoid of any effect on dopamine-induced cytotoxicity and nitrite production, whereas at higher expression (5 μg cDNA/10 5 cells), the variants enhanced dopamine-mediated effects. Low levels of wt α-synuclein blocked H 2O 2-induced cytotoxicity and nitrite production, a protective effect that was partly decreased upon higher expression. Both A30P and A53T increased in a dose-dependent manner H 2O 2-induced nitrite production and cell death. These results show an absence of protective effects for the A30P/A53T mutants, and a differential cytoprotective role of α-synuclein against oxidants, which varies according to expression levels.
Published Version
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