Parkinson's disease candidate gene prioritization based on expression profile of mid-brain dopaminergic neurons

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease. Degeneration of the midbrain dopaminergic (mesDA) neurons in the substantia nigra pars compacta (SNpc) region of the brain is the pathological hallmark of PD. Different types of transcriptional or other factors that mediate the generation, migration, and differentiation of mesDA neurons in SNpc, may undertake non-developmental roles in developed mesDA neurons, as several recent studies show that the mesDA neurons require such factors for survival and maintenance throughout life. The deficiency in these factors may also contribute to the vulnerability of SNpc neurons to degeneration, and may be causal to initiation and advancement of the disease. Several factors, including aging and exposure to environmental toxins, contribute to degeneration of this neuronal population and the identification of familial cases put genetics among such factors. This study takes advantage of the previous data to further understand the dynamics between the role of developmental factors, genetics and the classical etiology of the disease and to identify novel correlations between the genes with high expression levels in mesDA neurons and several processes within the SNpc. Utilizing the genes of known function in five categories of development, survival, genetics, pro-apoptosis and anti-apoptosis, and using two online software, ToppGene and Endeavour, I identified several genes which can be placed within each of these categories. The results of this study may be used in identification of novel molecular and biochemical processes, contributing to etiology of the disease, which may be used as new therapeutic targets.