Nanomolar concentration of alpha-synuclein enhances dopaminergic neuronal survival via Akt pathway

Although alpha-synuclein is generally thought to have a pathological role in Parkinson's disease, accumulative evidence exists that alpha-synuclein has a neuroprotective effect. The aim of this study was to evaluate the effect of extracellular alpha-synuclein on dopaminergic cell survival. We assessed cell viability using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltertazolium bromide (MTT) assay both in undifferentiated SH-SY5Y (SHSY) cells and neuronally-differentiated SH-SY5Y (ndSHSY) cells after 24 hour treatment with monomeric alpha-synuclein at various concentrations (0 [control], 50, 100 nmol/L, 1 μmol/L). To determine whether cell viability assessed by MTT assay was affected by cell proliferation, 5-bromo-2'-deoxyuridine (BrdU) incorporation assay was performed. Level of both Akt and phosphorylated Akt was measured using western blot method in ndSHSY cells with or without 24 hour alpha-synuclein treatment. Cell viability was increased in ndSHSY cells at the nanomolar concentration of alpha-synuclein, but not in SHSY cells. Proportion of BrdU-positive ndSHSY cells was decreased in alpha-synuclein-treated group compared with control group. Level of phosphorylated Akt in alpha-synuclein-treated group was higher compared with the control group. Our study shows that extracellular alpha-synuclein at nanomolar concentration benefits dopaminergic cell survival via Akt pathway.