Selective Vulnerability of Dopaminergic Neurons in Drosophila - Project Summary Each major neurodegenerative disease is associated with the loss of specific populations of neurons, yet very little is known regarding why these neurons are rendered vulnerable while others remain relatively resistant. In Parkinson’s Disease, for example, dopaminergic neurons within the Substantia Nigra are primarily lost while other nearby neurons remain unaffected. Understanding the mechanisms underlying this selective vulnerability should help to generate strategies for protective these vulnerable neurons from disease. Thus far, a major hurdle in the field has been the inability to assess the vulnerability of individually identifiable neurons in vivo. To address this, we have developed a proposed research plan to investigate the mechanisms responsible for maintaining Dopaminergic (DA) neuron viability within the Drosophila brain. Our guiding hypothesis is that conserved factors render specific populations of neurons vulnerable to Parkinson’s Disease while others remain resistant. To test this hypothesis, we propose to study the selective vulnerability of Drosophila DA neurons by: (1) Creating a vulnerability map of individual DA neurons in an environmental model of Parkinson’s Disease, (2) Manipulating the vulnerability status of individual DA neurons, and (3) Comparing vulnerability maps of different Parkinson’s Disease models. By investigating the cellular and molecular mechanisms underlying selective neuronal vulnerability, our proposed research has the potential to reveal why certain populations of neurons are rendered vulnerable. Understanding the differences between vulnerable and resistant neurons is critical for identifying potential therapeutic targets and developing strategies to help maintain vulnerable neurons and increase their resistance to disease.
