NOVEL USE OF A SUPEROXIDE RADICAL DISMUTATING AGENTS AS A THERAPEUTIC APPROACH TO HAMPER THE PROGRESSION OF PARKINSON’S DISEASE

Parkinson’s disease (PD) is an incurable, debilitating disorder characterized the preferential degeneration of dopaminergic neurons in the Substantia Nigra. Although PD is generally a sporadic neurological disorder, the discovery of monogenic, hereditable forms of the disease, representing 5–10% of all cases, has been very important in helping to partially delineate the molecular pathways that lead to this pathology. Oxidative damages and mitochondrial dysfunction are considered central in dopaminergic neurodegeneration. Considering that most of the intracellular reactive oxygen species derive from superoxide anion, in the present work we evaluated the potential protective effects of superoxide radical dismutating molecules, in both human SH-SY5Y neuroblastoma cell lines and Drosophila melanogaster flies. We first demonstrated the beneficial role of reducing superoxide anion accumulation against the toxicity induced by the herbicide paraquat, whose chronic exposure has been epidemiologically correlate to the onset of PD. Then, these findings were further validated in a genetic models of PD, based on PINK1 silencing. In conclusion our work indicates that the use of superoxide dismutating agents can be efficacious in reducing toxicity associated with oxidative stress and should be explored further as viable therapeutic agents to hamper the progression of PD.