Abstract: Objective To study the role of phosphorylation at Serine 129 in regulating the neurotoxicity of α-synuclein. Methods Wild type and phosphomimic mutant α-synuclein genes were over-expressed in mouse dopaminergic cells MN9D using retrovirus. The cell viability was examined using CCK-8 assay and the cell morphology was observed with immunofluorescence microscope. Results The result of real time PCR showed that WT/α-SYN and S129D/α-SYN genes were overexpressed in MN9D as compared to uninfected MN9D and vector control group. The cell viability was obviously reduced when over-expressing both WT and phosphorylated α-synuclein genes. And the viability of cells over-expressing wild type α-synuclein was much lower than that of the cells over-expressing phosphorylated α-synuclein. Insoluble α-synuclein aggregates were observed with confocal microscope in the MN9D cells over-expressing phosphorylated α-synuclein. Conclusion Over-expressing phosphorylated α-synuclein may lead to α-synuclein aggregated in MN9D cells. Phosphorylated at 129 Ser may protect the cells from toxicity induced by over expressing α-synuclein.

Key words: a-synuclein, phosphorylated α-synuclein, neurocyte protection, dopaminergic cells