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AG Title: BDNF rs6265 and Dopaminergic Neuron Vulnerability in Parkinson's Disease

AG Abstract: Parkinson's disease involves progressive degeneration of dopaminergic neurons and Lewy body formation, but factors influencing neuronal vulnerability remain unclear. The common BDNF rs6265 (Val66Met) variant reduces activity-dependent BDNF release and may influence Parkinson's disease progression. Using a novel knock-in rat model, we are investigating whether rs6265 alters dopaminergic neuron vulnerability to α-synuclein pathology. This work may provide insight into how common genetic variation influences susceptibility to Parkinson's disease.

AD Title: Effects of Roxadustat Treatment in Dystrophic Mice

AD Abstract: Duchenne muscular dystrophy (DMD) is a debilitating genetic disorder characterized by progressive muscle weakness and fatigue, loss of ambulation, cardiomyopathy, and early death—patients often die by age 30. Treatments options are available but are costly and incompletely effective. Our laboratory goal is to identify therapeutic alternatives to better treat this disease. One drug under investigation is Roxadustat, an activator of hypoxia inducible factor (HIF) which is a transcription factor important for regulating cellular metabolism as well as erythropoietin production during hypoxia. Preliminary research from our laboratory suggests that Roxadustat increases treadmill exercise capacity and decreases muscle fatigue in situ in dystrophic mice with no detectable change in cardiac function. However, the mechanisms behind these improvements are currently unknown. Because functional improvements were observed in vivo and in situ, these improvements may have been the result of contributions from at least three main physiological systems: the cardiorespiratory, skeletal, and circulatory systems. Our hypothesis is that the main effect of Roxadustat is due to a direct effect of the drug on HIF activation and metabolism in striated muscle. To test this hypothesis, I am determining whether HIF activation has occurred in these target tissues by using immunofluorescent staining and Western blotting to determine HIF and HIF target protein levels. These findings are important as they will further inform the therapeutic potential of Roxadustat in a mouse model of DMD.