Abstract

Parkinson’s Disease (PD) is one of the most prevalent neurodegenerative disorders, with the death of dopaminergic neurons causing a loss of movement. One cellular hallmark is 𝛼-Synuclein protein accumulation, potentially contributing to cellular dysfunction and death. While genetic mutation can cause PD, most cases are sporadic. However, environmental and immunologic agents, like toxin exposure and gut dysbiosis, may initiate or worsen phenotypes. Therefore, interactions between genetics and environment are crucial for understanding PD etiologies. Moreover, gut microbiota dysregulation may induce 𝛼-Synuclein aggregation and release toxins that could increase oxidative stress, thereby causing dopamine neuron loss via the gut-brain axis. In the Drosophila melanogaster fly, oxidative stress induced by paraquat exacerbates Gram-negative bacterial infection, increasing mortality rates. The Chinese fruit Ziziphus jujuba has antioxidant and antimicrobial properties. This proposal will determine the optimal dose of Z. jujuba to reduce oxidative stress following paraquat exposure in wildtype Drosophila, using a Superoxide dismutase Assay. A Drosophila PD model exposed to paraquat will then be infected with bacteria in order to test Z. jujuba’s antimicrobial potential, measured using bacterial counts. Ultimately, dopamine neuron protection and motor function can be assessed. It is predicted that the combined antioxidant and antimicrobial capacities will provide enhanced protection against oxidative stress and bacterial infection. Given the role of the gut-brain axis in PD, reducing gut bacterial infection and oxidative stress may preserve dopamine neurons. Most PD treatments simply target motor symptoms. This proposal is significant to the field as it may reduce dopamine neuron death that underlies PD.