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ATP Exposure Increases Expression of α‐Synuclein in SH‐SY5Y Cells: Potential Link Between Neuronal Injury and Parkinson's Disease

Parkinson's disease (PD) is a devastating neurodegenerative disorder for which there is presently no cure. The pathologic hallmark of PD is intra‐neuronal accumulation of the protein α‐synuclein (α‐syn), and in rare instances, PD has been directly linked to multiplication of the α‐syn gene locus, suggesting that overexpression of α‐syn is pathogenetic per se. It has been suggested that α‐syn aggregation is increased in cells exposed to ATP, a condition known to arise during traumatic brain injury. These results suggest a potential link between neuronal injury, purinergic signaling, and the pathogenesis of PD, yet there remains limited information about this phenomenon. The primary goal of this project was to test the effect of ATP exposure on intracellular expression and extracellular secretion of α‐syn in mammalian cells. In preliminary studies, SH‐SY5Y cells treated for 24h with 1mM or 3mM ATP expressed higher levels of α‐syn protein, as measured by Western blot. However, these concentrations of ATP also slightly reduced cell viability at 24h, as measured by CellTiter‐Blue® assay. These results further support the proposed link between purinergic signaling and PD pathogenesis. These and future studies will provide much needed insight into the role of purinergic signaling in PD and could help identify novel therapeutic targets for the treatment of PD.