Parkinson's disease, pesticides and individual vulnerability

Current theories suggesting that degeneration of the nigrostriatal pathway following pesticide exposure could be a cause of Parkinson's disease (PD) are supported by epidemiological data linking environmental factors to an increased risk of parkinsonism. PD in humans is therefore thought to be a function of genetic predisposition, potentially associated with how efficiently an individual is able to metabolize dopamine-related neurotoxins. However, meta-analyses of susceptibility studies have failed to demonstrate clear-cut links between polymorphisms of xenobiotic-metabolizing enzymes (XMEs) and PD. We hypothesize that PD-related vulnerability to pesticides is linked to a strictly personal 'chemico-genetic XME blend' involving many variables. Innate XME genetic fingerprints undergo acquired 'modulations', which in turn are influenced by a myriad of individual exposures to chemical mixtures of environmental pollutants. We make a series of suggestions for the design of susceptibility studies focusing on persistent exposure to a specific pesticide in genetically defined population subsets of workers and gardeners within a geographically defined area.