Gene-environment interactions in sporadic Parkinson's disease

Liat BenMoyal-Segal, Hermona Soreq*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

60 Scopus citations

Abstract

Much has been learned in recent years about the genetics of familial Parkinson's disease. However, far less is known about those malfunctioning genes which contribute to the emergence and/or progression of the vast majority of cases, the 'sporadic Parkinson's disease', which is the focus of our current review. Drastic differences in the reported prevalence of Parkinson's disease in different continents and countries suggest ethnic and/or environmental- associated multigenic contributions to this disease. Numerous association studies showing variable involvement of multiple tested genes in these distinct locations support this notion. Also, variable increases in the risk of Parkinson's disease due to exposure to agricultural insecticides indicate complex gene-environment interactions, especially when genes involved in protection from oxidative stress are explored. Further consideration of the brain regions damaged in Parkinson's disease points at the age-vulnerable cholinergic-dopaminergic balance as being involved in the emergence of sporadic Parkinson's disease in general and in the exposure-induced risks in particular. More specifically, the chromosome 7 ACHE/PON1 locus emerges as a key region controlling this sensitive balance, and animal model experiments are compatible with this concept. Future progress in the understanding of the genetics of sporadic Parkinson's disease depends on globally coordinated, multileveled studies of gene-environment interactions.

Original languageEnglish
Pages (from-to)1740-1755
Number of pages16
JournalJournal of Neurochemistry
Volume97
Issue number6
DOIs
StatePublished - Jun 2006

Keywords

  • Acetylcholinesterase
  • Inherited susceptibility
  • Insecticide exposure
  • Multigene contributions
  • Paraoxonase 1

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