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The Journal of Neuroscience, June 27, 2007, 27(26):6914-6922; doi:10.1523/JNEUROSCI.1569-07.2007

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Neurobiology of Disease
Iron and Paraquat as Synergistic Environmental Risk Factors in Sporadic Parkinson's Disease Accelerate Age-Related Neurodegeneration

Jun Peng,¹ Li Peng,² Fang Feng Stevenson,¹ Susan R. Doctrow,³ and Julie K. Andersen¹

¹Buck Institute for Age Research, Novato, California 94945, ²Telstra Burns and Reconstruction Unit, Royal Perth Hospital, Perth, Washington 6847, Australia, and ³Proteome Systems, Woburn, Massachusetts 01801

Correspondence should be addressed to Julie K. Andersen, Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945. Email: jandersen{at}buckinstitute.org

Extensive epidemiological data in humans and studies in animal models of Parkinson's disease (PD) suggest that sporadic forms of the disorder are not strictly genetic in nature but most likely because of combined environmental exposures over the period of the life-span coupled with increased genetic susceptibilities. Environmental paraquat and neonatal iron exposure have both been separately suggested as potential risk factors for sporadic forms of the disease. In this study, we demonstrate that combined environmental exposure to these two agents results in accelerated age-related degeneration of nigrostriatal dopaminergic neurons. Furthermore, pretreatment with the synthetic superoxide dismutase/catalase mimetic, EUK-189, significantly attenuated neuronal death mediated by combined paraquat and iron treatment. These findings support the notion that environmental PD risk factors may act synergistically to produce neurodegeneration associated with the disorder and that iron and paraquat may act via common oxidative stress-mediated mechanisms.

Key words: dopaminergic neurons; iron; paraquat; Parkinsonism; risk factors; sporadic

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Received Feb. 7, 2007; revised May 14, 2007; accepted May 15, 2007.

Correspondence should be addressed to Julie K. Andersen, Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945. Email: jandersen{at}buckinstitute.org

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