Rotenone and paraquat perturb dopamine metabolism: A computational analysis of pesticide toxicity.

ABSTRACT: Pesticides, such as rotenone and paraquat, are suspected in the pathogenesis of Parkinson's disease (PD), whose hallmark is the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Thus, compounds expected to play a role in the pathogenesis of PD will likely impact the function of dopaminergic neurons. To explore the relationship between pesticide exposure and dopaminergic toxicity, we developed a custom-tailored mathematical model of dopamine metabolism and utilized it to infer potential mechanisms underlying the toxicity of rotenone and paraquat, asking how these pesticides perturb specific processes. We performed two types of analyses, which are conceptually different and complement each other. The first analysis, a purely algebraic reverse engineering approac

SUBMITTER: Qi Z 

PROVIDER: S-EPMC3893822 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature