Abstract
This chapter describes a model of Parkinson's disease (PD) risk factors generated by exposure to the herbicide paraquat. Recent studies show that paraquat is a toxin that damages the nigrostriatal system and reproduces neurodegenerative changes relevant to PD. Whether or not paraquat itself acts as a risk factor and contributes to disease development in humans remains is to be established. As a model of environmental exposure targeting the nigrostriatal system, paraquat administration has enhanced understanding of toxic processes/mechanisms that could underlie the action of PD risk factors and the pathogenesis of neurodegeneration in PD. The mechanistic studies using the paraquat model bear important implications for the development of PD therapeutics. Paraquat toxicity could be a model of choice for investigating preclinical lesions, elucidating mechanisms of neuronal vulnerability, and testing agents for neuroprotection against moderate nigrostriatal injury. The chapter reviews the features of the presented model with the intent of highlighting mechanisms of likely relevance to the role of environmental exposures and gene–environment interactions in PD.
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