Overexpression of alpha-synuclein promotes both cell proliferation and cell toxicity in human SH-SY5Y neuroblastoma cells

Abstract

Alpha-Synuclein (aSyn) is a chameleon-like protein. Its overexpression and intracellular deposition defines neurodegenerative alpha-synucleinopathies including Parkinson's disease. Whether aSyn upregulation is the cause or the protective reaction to alpha-synucleinopathies remains unresolved. Remarkably, the accumulation of aSyn is involved in cancer. Here, the neuroblastoma SH-SY5Y cell line was genetically engineered to overexpress aSyn at low and at high levels. aSyn cytotoxicity was assessed by the MIT and vital-dye exclusion methods, observed at the beginning of the sub-culture of low-aSyn overexpressing neurons when cells can barely proliferate exponentially. Conversely, high-aSyn overexpressing cultures grew at high rates while showing enhanced colony formation compared to low-aSyn neurons. Cytotoxicity of aSyn overexpression was indirectly revealed by the addition of pro-oxidant rotenone. Pretreatment with partially reduced graphene oxide, an apoptotic agent, increased toxicity of rotenone in low-aSyn neurons, but, it did not in high-aSyn neurons. Consistent with their enhanced proliferation, high-aSyn neurons showed elevated levels of SMP30, a senescence-marker protein, and the mitosis Ki-67 marker.