title: Age-environment and gene-environment interactions in the pathogenesis of Parkinson's disease.
abstract: Parkinson's disease (PD) is a common neurodegenerative disease characterized by dopaminergic cell death and deposition of Lewy bodies within the substantia nigra of the midbrain. Although the major risk factors for PD are aging and environmental factors, there is an important genetic component. An age-related change in xenobiotic metabolism alters the metabolism of and net exposure to, environmental neurotoxins. Genetic variability in xenobiotic metabolism may similarly increase the susceptibility to PD by altering the metabolism of neurotoxins. Genetic studies of rare familial cases of PD indicate a central mechanistic role for the aggregation of alpha-synuclein, a protein found in Lewy bodies. Environmental factors like pesticides and heavy metals can also influence alpha-synuclein aggregation. Common final pathways for aging, environmental, and genetic mechanisms can thus exist, involving both direct neurotoxicity and alpha-synuclein aggregation.
authors.affiliation: Centre for Education and Research on Ageing and the Anzac Research Institute, University of Sydney, Concord RG Hospital, NSW, Australia. dlecouteur@med.usyd.edu.au
authors.forename: David G
authors.initials: DG
authors.lastname: Le Couteur
authors.forename: Michael
authors.initials: M
authors.lastname: Muller
authors.forename: Maria C
authors.initials: MC
authors.lastname: Yang
authors.forename: George D
authors.initials: GD
authors.lastname: Mellick
authors.forename: Allan J
authors.initials: AJ
authors.lastname: McLean
mesh_terms: D000375:Aging; D004781:Environmental Exposure / Q000009:adverse effects / Q000032:analysis; D006801:Humans; D009498:Neurotoxins / Q000009:adverse effects / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015262:Xenobiotics / Q000009:adverse effects / Q000378:metabolism
chemical_list: D009498:Neurotoxins; D015262:Xenobiotics