Article

Iron and paraquat as synergistic environmental risk factors in sporadic Parkinson's disease accelerate age-related neurodegeneration

Royal Perth Hospital, Perth City, Western Australia, Australia
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 07/2007; 27(26):6914-22. DOI: 10.1523/JNEUROSCI.1569-07.2007
Source: PubMed

ABSTRACT 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.

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    • "Contrary to normal subjects, where more Fe 2+ is deposited in the SN pars reticulata, in PD Fe 2+ is deposited abundantly in the SNpc containing pigmented neurons (Sian-Hulsmann et al., 2011). Together with paraquat, Fe 2+ enhances dopaminergic neurodegeneration (Peng et al., 2007). Low levels of ferritin in the SNpc of PD patients and incidental Lewy body disease cases have been reported. "
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    • "This TF-TFR2 mediated mitochondrial mechanism of pathology is likely to be only one of a number of factors contributing to PD pathology. Given that iron excess (or iron depletion) in model systems aggravates (or attenuates) pesticide toxicity (e.g., Kaur et al., 2003; Peng et al., 2007 "
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    • "However, in PD patients the ratio of reduced to oxidized iron in the SN has been reported to increase [48], in one report to 1:3 [49]; a dysregulation not found in other tissues or regions of the brain [49] [50]. Because numerous studies have shown that the elevated levels of reduced iron in the SN can lead to cellular toxicity [51] [52] [53] [54], it has been suggested that iron chelation may provide some level of neuroprotection in Parkinson disease [55] [56] [57] [58]. "
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