Early environmental origins of neurodegenerative disease in later life.
Landrigan PJ, Sonawane B, Butler RN, Trasande L, Callan R, Droller D.
Environ Health Perspect. 2005 Sep;113(9):1230-3.
Center for Children's Health and the Environment, Department of Community
and Preventive Medicine, Mount Sinai School of Medicine, New York, NY 10029,
USA. [log in to unmask]
Parkinson disease (PD) and Alzheimer disease (AD), the two most common
neurodegenerative disorders in American adults, are of purely genetic origin
in a minority of cases and appear in most instances to arise through
interactions among genetic and environmental factors. In this article we
hypothesize that environmental exposures in early life may be of particular
etiologic importance and review evidence for the early environmental origins
of neurodegeneration. For PD the first recognized environmental cause, MPTP
(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), was identified in
epidemiologic studies of drug abusers. Chemicals experimentally linked to PD
include the insecticide rotenone and the herbicides paraquat and maneb;
interaction has been observed between paraquat and maneb. In epidemiologic
studies, manganese has been linked to parkinsonism. In dementia, lead is
associated with increased risk in chronically exposed workers. Exposures of
children in early life to lead, polychlorinated biphenyls, and methylmercury
have been followed by persistent decrements in intelligence that may presage
dementia. To discover new environmental causes of AD and PD, and to
characterize relevant gene-environment interactions, we recommend that a
large, prospective genetic and epidemiologic study be undertaken that will
follow thousands of children from conception (or before) to old age.
Additional approaches to etiologic discovery include establishing incidence
registries for AD and PD, conducting targeted investigations in high-risk
populations, and improving testing of the potential neurologic toxicity of
chemicals.
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Cell Tissue Res. 2004 Oct;318(1):225-41. Epub 2004 Jul 16.
Neurotoxicant-induced animal models of Parkinson's disease: understanding
the role of rotenone, maneb and paraquat in neurodegeneration.
Uversky VN.
Institute for Biological Instrumentation, Russian Academy of Sciences,
142290 Pushchino, Moscow Region, Russia. [log in to unmask]
The etiologic basis of Parkinson's disease (PD), the second most common
age-related neurodegenerative disorder, is unknown. Recent epidemiological
and experimental studies indicate that exposure to environmental agents,
including a number of agricultural chemicals, may contribute to the
pathogenesis of this disorder. Animal models are important tools in
experimental medical science for studying the pathogenesis and therapeutic
intervention strategies of human diseases. Since many human disorders do not
arise spontaneously in animals, characteristic functional changes have to be
mimicked by neurotoxic agents. Recently, agricultural chemicals, when
administrated systemically, have been shown to reproduce specific features
of PD in rodents, thus opening new routes for the development of animal
models for this disorder. In addition to a brief historical overview of the
toxin-induced PD models, this study provides a detailed description of
exiting models in which Parkinsonism is initiated via the exposure of
animals to such agricultural chemicals as rotenone, paraquat, and maneb.
Suggested neurotoxicity mechanisms of these chemicals are considered, and
the major lessons learned from the analysis of pesticide-induced PD models
are discussed.
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Lancet Neurol. 2003 Sep;2(9):531-8.
The environment and Parkinson's disease: is the nigrostriatal system
preferentially targeted by neurotoxins?
Di Monte DA.
Parkinson's Institute, Sunnyvale, CA 94089, USA.
[log in to unmask]
Recent epidemiological and experimental studies have renewed interest in the
hypothesis that the environment has a role in the pathogenesis of
Parkinson's disease (PD). Epidemiological studies have identified protective
associations (eg, smoking) as well as adverse risk factors (eg, pesticide
exposure) for PD. The concordance rate of PD in pairs of dizygotic twins is
similar to that in pairs of monozygotic twins, supporting a role of
non-genetic risk factors. New models of selective nigrostriatal damage--such
as neurotoxicity induced by rotenone or paraquat--have emphasised that
environmental agents may contribute to the neurodegenerative process in PD.
Toxins interact, in vitro and in vivo, with alpha-synuclein, an endogenous
protein that is implicated in pathology of PD. Similarities between clinical
and experimental findings, such as the role of pesticide exposure as a
potential environmental risk factor, highlight the importance of a
multidisciplinary approach to the aetiology of PD.
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