The pathogenesis of neurodegenerative disease: neurotoxic mechanisms of action and genetics.

The role of environmental and occupational exposures to neurotoxicants in the pathogenesis of neurodegenerative disease has not been fully elucidated. Recent published research on whether genetic polymorphisms contribute to individual susceptibility to develop neurodegenerative diseases such as Parkinson's disease have been equivocal at best. This review relates putative mechanisms of neurotoxicant-induced cell damage to polymorphisms in the genes that encode for the enzymes involved in the metabolism of neurotoxicants. The effects that genetically induced alterations in enzyme functioning have on neurotoxicant metabolism and how this relates to the risk of neurotoxic effects among exposed individuals are reviewed. A pragmatic approach to future research in the area of neurodegenerative disease is developed on the basis of the interrelationship between known routes of neurotoxicant metabolism and human genetics.