Post-translation modification of alpha-synuclein by oxidative stress in differentiated human neuroblastoma cells

Alpha-synuclein is known to be a brain presynaptic protein and to be a structural component of the filaments in Lewy bodies in Parkinson’s disease brains and other neurodegenerative disorders. Alpha-synuclein has been found to be phosphorylated on serine 129 in Lewy bodies. The phospho- serine 129 alpha-synuclein promotes fibril formation in vitro, suggesting the importance of phosphorylation of the filamentous protein in the pathogenesis of Parkinson’s disease. Recent findings of abnormal protein folding, coupled with oxidative stress, provide scientific rationale for studies designed to characterize the effect of oxidative stress on alpha-synuclein post-translation modifications. We report here that oxidative stress, induced by the pro-oxidant pair iron-ascorbate, modulates the phosphorylation state of alpha-synuclein as detected by Western blot analysis using specific phospho-antibodies and modified the intracellular distribution of this protein in differentiated SH-SY5Y cells. These results demonstrated that oxidative stress induced post-translation modification of the alpha-synuclein protein supporting the notion of the role of oxidative stress in neurodegenerative disease characterized by alpha-synuclein positive lesions. Supported by the University of Bologna, Funds for Selected Research Topics.