Abstract:
Dopamine, a critical neurotransmitter, regulates dozens of vital biological functions within the human brain and throughout the body, and therefore disruptions in dopamine signaling result in a wide range of behavioral, psychological and movement-related disorders. In this report, we evaluate the role of dopamine production and trafficking in two of the most common neurological movement disorders, Parkinson’s disease and Torsion Dystonia. As we age, a naturally occurring process known as neurodegeneration results in the gradual loss of neuron structure and function over time. Due to this compromised cellular integrity, neurons become considerably more susceptible to oxidative stress, mitochondrial damage, and protein misfolding and aggregation. In Parkinson’s disease and many other neurodegenerative disorders, aging remains the greatest factor contributing to disease onset. In both Parkinson’s disease and Dystonia, dopamine regulation is significantly altered, causing severe motor and mobility defects. Here, we use the model system Drosophila melanogaster to investigate genetic, environmental and dietary factors contributing to the disruption of dopamine signaling and transmission. We also present a novel method for the quantification of cellular signals related to neuroinflammation, a sophisticated immune cascade activated in the central nervous system in response to neuron stress or damage. Our work has not only proved robust evidence for the validation of our previously published results, but has also introduced novel genetic interactions and molecular pathway that strongly influence the development and progression of Parkinson’s disease and Dystonia pathology. More broadly, these findings contribute new insight into the mechanistic networks contributing to the general understanding of dopamine regulation and disorders.
