Modeling Crosstalk of Tau and ROS Implicated in Parkinson’s Disease Using Biochemical Systems Theory

The application of systems theory to complex biological systems helps to rebuild complex biochemical reactions to study interactions between small biomolecules and how their dysfunctions lead to Parkinson’s disease (PD) and other complex diseases. Modeling of cellular pathways using biochemical system theory helps to reconstruct the biochemical reactions involving major proteins and their interactions inside a cell. In this study, two important pathways involved in Parkinson’s disease have been modeled: cellular interactions related to tau protein and role of reactive oxygen species. The experimental data for initial conditions for the model was extracted from literature for both normal and diseased conditions. The model helped to understand the dynamic behavior of cellular components and their interactions that regulate the emergent properties of the system based on ordinary differential equations and kinetics laws. The results have shown that mutations in several important genes related to Parkinson’s including SNCA, DJ-1, tau can cause abnormal protein aggregation, mitochondrial disruption, disturbed cell homeostasis that trigger various cell death pathways. The model suggests possible biomarkers related to PD that help to find potential therapeutic targets for early diagnosis and predicting disease progression.