Environmental toxicants and Parkinson's disease: recent evidence, risks, and prevention opportunities.

The global burden of Parkinson's disease is rising. Large-scale genetic studies have confirmed that extrinsic or environmental factors, rather than genetic predisposition, play a dominant role in its cause. Increasing evidence implicates three classes of toxicants-certain pesticides, the dry-cleaning chemicals trichloroethylene and perchloroethylene, and air pollution-in the development of Parkinson's disease. These toxicants are widely prevalent, impair mitochondrial or lysosomal function, or both, and contribute to, if not cause, the disease. Parkinson's disease could be thus largely preventable. Uncertainties remain regarding the relevant doses, timing, and routes of exposure, the nature of genetic and environmental interactions, the effects of combined exposures, the role of the microbiome, and the identity of other environmental risks. Methodological limitations and structural challenges hinder our understanding. However, improved measurement of toxicant exposure in individuals and the environment, long-term prospective studies, increased funding for prevention, and policy changes can precipitate the fall of the burden of Parkinson's disease.