Age-environment and gene-environment interactions in the pathogenesis of Parkinson's disease

Rev Environ Health. 2002 Jan-Mar;17(1):51-64. doi: 10.1515/reveh.2002.17.1.51.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging
  • Environmental Exposure / adverse effects
  • Environmental Exposure / analysis
  • Humans
  • Neurotoxins / adverse effects
  • Neurotoxins / metabolism
  • Parkinson Disease / etiology*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Xenobiotics / adverse effects
  • Xenobiotics / metabolism

Substances

  • Neurotoxins
  • Xenobiotics