Computational modelling of apoptosis in parkinson's disease using biochemical systems theory

摘要

In this study, we present a computational model of Parkinson's disease (PD) that includes different biological interactions that leads to neural cell death with the use of biochemical systems theory. The model incorporates a set of important pathways in PD including dopaminergic pathway, mitochondrial pathway and P53 - DNA damage pathway. Modeling signaling pathways and simulations were performed using biochemical systems theory. Initial concentrations have been taken from experimental data in literature and were used to model the changes. Results generated by dopaminergic diseased pathway show 45% decrease in dopamine, compared to normal condition. In addition, the activity of MOMP, Caspase 9 and Apoptosome expression in diseased condition within mitochondrial pathway model have been observed in the results. The expression levels of BAX and MOMP were reconstructed and simulations suggest oligomerization of BAK leads to the elevation of MOMP. An increase in oxidative stress and apoptosis level also has been observed in the PD condition, compared to the control allowing comparisons between normal and diseased conditions with these mathematical models.