Gene-environment interactions in Parkinson's disease and other forms of parkinsonism

Jeffery M. Vance, Syed Ali, Walter G. Bradley, Carlos Singer, Donato A. Di Monte

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

It is widely recognized that both genetic and environmental factors are likely to contribute to the pathogenesis of human parkinsonism. While the identification of specific predisposing conditions and mechanisms of disease development remain elusive, new discoveries coupled with technological advances over the past decade have provided important clues. From the genetic standpoint, both causal and susceptibility genes have been identified, with some of these genes pointing to gene-environment interactions. The application of emerging genomic technologies, such as Genome Wide Association Studies (GWAS), will certainly further our knowledge of Parkinson's disease (PD)-related genes. From the environmental perspective, toxicant-induced models of parkinsonian syndromes, such as those associated with exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or β-N-methylamino- l-alanine (BMAA), have revealed potential mechanisms of increased susceptibility based on genetic predisposition. Finally, new hypotheses on mechanisms of disease development include the possibility that exposure to neurotoxicants triggers an upregulation and pathological modifications of α-synuclein. Mutations in the α-synuclein gene are responsible for rare familial cases of parkinsonism, and polymorphisms in the promoter region of this gene confer a higher susceptibility to idiopathic PD. Thus, toxicant-α-synuclein interactions could have deleterious consequences and play a role in pathogenetic processes in human parkinsonism.

Original languageEnglish (US)
Pages (from-to)598-602
Number of pages5
JournalNeurotoxicology
Volume31
Issue number5
DOIs
StatePublished - Sep 1 2010

Keywords

  • Cyanobacteria
  • Genome
  • MPTP
  • Neurotoxicant
  • Parkinson
  • Synuclein

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Fingerprint Dive into the research topics of 'Gene-environment interactions in Parkinson's disease and other forms of parkinsonism'. Together they form a unique fingerprint.

  • Cite this