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PMID: 17596439 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 27 ·No. 26 ·2007-06-27 ·Pages 6914-22

Peng J, Peng L, Stevenson FF, Doctrow SR, Andersen JK

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.

MeSH Terms
Aging/metabolism,pathology Animals Cell Line Cells, Cultured Drug Synergism Environmental Exposure/adverse effects Herbicides/toxicity Iron/toxicity Male Mice Mice, Inbred C57BL Nerve Degeneration/etiology,metabolism,physiopathology Neurons/drug effects,metabolism,pathology Neuroprotective Agents/pharmacology Organometallic Compounds/pharmacology Paraquat/toxicity Parkinson Disease/etiology,metabolism,physiopathology Rats Salicylates/pharmacology Substantia Nigra/drug effects,pathology,physiopathology Superoxide Dismutase/metabolism
Chemicals
EUK-189 Herbicides Neuroprotective Agents Organometallic Compounds Salicylates Iron Superoxide Dismutase Paraquat
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Peng Jun
Buck Institute for Age Research, Novato, California 94945, USA.
Peng Li
Stevenson Fang Feng
Doctrow Susan R
Andersen Julie K
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.1569-07.2007
Published
2007-06-27
Pages
6914-22
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6672233
Subset
IM
Grants
NIEHS NIH HHS · U54 ES012077 · United States
NIEHS NIH HHS · U54 ES12077 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.1569-07.2007 PMC Full Text View journal details
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