Funded Studies
Study Rationale: Parkinson’s disease (PD) is associated with the death of dopamine-producing neurons. Neuroprotective strategies that could maintain these critical cells would provide a much-needed approach to the treatment of PD. One gene that has been associated with PD-associated neurodegeneration and therefore presents a potentially targetable for neuroprotection is Atp6v0a. The gene encodes a component of a molecular pump associated with the lysosome, a structure thought to malfunction in PD. In this study, we will determine whether modulating the activity of the Atp6v0a1 gene will influence cell function and the progression of cell death in isolated neurons and preclinical models of PD.
Hypothesis: We predict that reducing the activity of the gene Atp6v0a1 will be neuroprotective and that elevating its activity will be toxic in isolated neurons and in preclinical models of PD.
Study Design: The impact of manipulating the activity of Atp6v0a1 on neuronal function and survival will be assessed using isolated neurons and preclinical models of PD that involve abnormal accumulation of alpha-synuclein.
Impact on Diagnosis/Treatment of Parkinson’s disease: If repression of Atp6v0a1 gene activity prevents neuronal cell death, inhibiting the activity of v-ATPase— the molecular pump encoded, in part, by the Atp6v0a1 gene—could be neuroprotective in PD.
Next Steps for Development: Subsequent studies could focus on testing and optimizing the neuroprotective effects of existing v-ATPase inhibitors in models of PD.