DEVELOPMENT OF NEW DRUGS TO INHIBIT NEURODEGENERATION OF DOPAMINE NEURONS: A lipidomic study in Parkinson’s disease cell models

Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder, pathologically characterised by the specific loss of dopaminergic (DAergic) neurons in the substantia nigra (SN) and the formation of aggregate structures known as Lewy bodies in surviving neurons. Mitochondrial dysfunction, oxidative stress and apoptosis are some are the factors thought to contribute to cell death in PD, however its etiology remains largely unknown. Recently there has been a focus on lipids and their role in signaling pathways involved in neuronal survival and neurodegeneration. Lipids are an incredibly diverse group of compounds that have a vast range of important biological functions, including being the major structural components of cell membranes, acting as energy storage sources and as signaling molecules in a number of cellular pathways. Lipidomics is a rapidly developing field of research, given the crucial roles of lipids in the control and regulation of various cell functions and diseases. The vast improvements of high-throughput lipidomics in recent years have allowed qualitative and quantitative analyses of these complex molecules to be achieved. This thesis demonstrates a lipidomic analysis of neuronal cells and compares the lipid profiles of various cell models of PD. It introduces a novel method of investigating toxicity in various cell models of PD and demonstrates that “disease-state” and “normal” cells can be distinguished from one another purely on the basis of their lipid profiles. The potential therapeutic benefits of omega-3 polyunsaturated fatty acids on neurotoxicity are also explored.