Neuron diversity and vulnerability in neurodegenerative disease

Neurodegenerative diseases, including Alzheimer’s and Parkinson’s, are devastating disorders affecting millions worldwide. All aging populations worldwide are increasing. With the population increase, the aging population in Africa is growing and is estimated to surpass 105 million by 2030. As neurodegenerative disease mainly affects the elderly, this increase constitutes a major financial challenge for societies worldwide. The degeneration of dopamine-producing neurons is a hallmark of Parkinson’s disease (PD) and a cause of many of the severe motor symptoms characteristic of the disease. Although it is well known that these neurons are diverse and that different subtypes display different vulnerabilities in PD pathology, the mechanisms underlying these differences remain unknown. Elucidating such mechanisms at the molecular level is of importance for the development of drugs and is the focus of my project. We are studying dopamine neurons by taking advantage of newly developed techniques for analyses of cells at the single-cell level. We are using these techniques to study dopamine neurons in mice, in genetically altered mice with a PD-like disease affecting their dopamine neurons, and in human brain tissue from healthy controls and PD patients. Our preliminary results have identified new potential drug targets using the single-cell methodology. The current project aims for a more detailed analysis that will expand and refine the studies to develop therapeutic strategies for treating PD.