Zhen Qi, Gary Miller, Eberhard Voit
Pesticides like rotenone and paraquat are suspected as contributors to Parkinson’s disease, for which a primary trait is the loss of dopaminergic neurons over the course of the disease. Through this study, Qi et al developed a mathematical model of dopamine metabolism to help identify how rotenone and paraquat could be disrupting these specific processes. The authors took two computational approaches to address this question. The first approach worked to identify what the enzyme activities would look like if the pesticides were impacting dopamine metabolism. The other method identified possible mechanisms through which pesticides could be acting. The approaches identified rotenone and paraquat acting in dopamine metabolism and suggested several specific mechanisms through which they could be acting without a priori assumptions. The study demonstrates how computational systems biology approaches can serve as key tools in identifying mechanisms of toxicity due to pesticide exposures.