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Ironjustic
Fri, Mar-07-08, 17:16
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

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

http://www.jneurosci.org/cgi/content/full/27/26/6914

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