Development of a Novel Treatment Strategy to Treat Parkinsonian Neurodegeneration by Targeting Both Lewy Body Aggregation and Dopaminergic Neuronal Degradation in a Drosophila melanogaster Model

Parkinson’s Disease (PD) is characterized by the progressive degradation of dopaminergic neurons in the substantia nigra of the brain and is triggered by both environmental and genetic factors. PD is characterized by symptoms that can range from muscle dysfunction to severe mood disturbances. The pathology of PD is two-fold: (1) degradation of dopaminergic neurons due to mitochondrial calcium overload and (2) deposits of α-synuclein that increase cytosolic calcium levels in the brain. In this study, we tested a therapy that targets both pathologic manifestations of PD in fruit flies. Specifically, we used combinations of the drugs Ruthenium red (RuR), a mitochondrial channel uniporter inhibitor, and Ambroxol, a pharmacological chaperone of the lysosomal enzyme glucocerebrosidase that digests α-synuclein, to treat PD in fruit flies. We then measured the climbing ability, ATP content, and glucocerebrosidase activity in the fruit flies. While the drugs showed positive results individually, we found that the drugs had a synergistic effect when used together that resulted in a statistically significant increase in climbing ability, ATP content, and glucocerebrosidase activity. The results of this study indicate that these drugs could be used in treatments for PD.