Importance of Synaptic vesicle trafficking dysfunction in Parkinson's disease

Parkinson's disease (PD) is the most common neurodegenerative movement disorder disease. PD's main pathological characteristic is the extensive and progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta and neuronal loss in different brain regions. Recent studies have shown that genetic and environmental factors have a role in the etiology of Parkinson's disease, but the exact mechanism is yet to be determined. In this work, I examined the evolutionary correlation of the genes associated with the genetics of PD to identify novel molecular pathways for Parkinson's disease. Phylogenetic profiling of 15 PD genes revealed a high degree of correlation among five genes, indicating potential participation in a common pathway. A literature review showed that all five genes have a role in synaptic vesicle trafficking, which could be a crucial pathological pathway in Parkinson's disease. To further investigate the connections between the genetics of PD and synaptic vesicle trafficking, I chose six genes that displayed the highest degree of correlation with the highest number of PD genes, based on the predicted linkages. Gene ontology analysis of these candidate proteins confirmed their involvement in synaptic vesicle trafficking. These results suggested a strong connection between the proteins involved in the regulation of synaptic vesicle trafficking and the etiology of Parkinson's disease.