title: The perplexing paradox of paraquat: the case for host-based susceptibility and postulated neurodegenerative effects.
abstract: Paraquat is an herbicide used extensively in agriculture and has also been proposed to be a risk factor for Parkinson's disease. To date, experimental, clinical, and epidemiological data on paraquat neurotoxicity have been equivocal. In this short review, we discuss some technical and biological mechanisms that contribute to inconsistencies regarding paraquat neurotoxicity. We hypothesize that individual genetic variations in susceptibility generate major differences in neurotoxic risk and functional outcome. Identifying these heritable sources of variation in host susceptibility, and their role in complex gene-environment interactions, is crucial to identify risk biomarkers and to devise better prevention and treatment for those exposed to paraquat and other potential neurotoxicants.
authors.affiliation: Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, USA; Department of Pharmacology, The Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA, USA. bcj1@psu.edu.
authors.forename: Byron C
authors.initials: BC
authors.lastname: Jones
authors.forename: Xuemei
authors.initials: X
authors.lastname: Huang
authors.forename: Richard B
authors.initials: RB
authors.lastname: Mailman
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
mesh_terms: D004785:Environmental Pollutants / Q000633:toxicity*; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000235:genetics; D010269:Paraquat / Q000633:toxicity*
chemical_list: D004785:Environmental Pollutants; D006540:Herbicides; D010269:Paraquat
keywords: Complex Traits; Host Susceptibility; Iron, Neurodegeneration; Paraquat; Parkinson's Disease; Toxicogenetics