Environmental Exposures and Parkinson's Disease Risk

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by the selective loss of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein aggregates. While monogenic forms of PD have revealed fundamental molecular pathways, most cases are idiopathic and reflect interactions between genetic susceptibility and environmental exposures. A growing body of epidemiological research links PD risk to pesticides, industrial solvents, heavy metals and air pollutants, with underlying mechanisms that include oxidative stress, mitochondrial impairment, neuroinflammation and protein misfolding. Exposure pathways span agricultural application, contaminated food and water, urban pollution and occupational contact. A nuanced appreciation of dose–response dynamics, critical periods of vulnerability and combined (“cocktail”) exposures is vital for developing preventive strategies and guiding environmental policy to mitigate neurotoxic risk.

Research from Nature Portfolio

Recent studies have combined large-scale pesticide-wide association analyses, leveraging agricultural records and health registries, with patient-derived induced pluripotent stem cell (iPSC) models to pinpoint compounds linked to PD. One investigation screened nearly three hundred pesticides, identifying over fifty associated with elevated PD incidence and, through live-cell imaging of iPSC-derived dopaminergic neurons, narrowed this to ten agents that induce selective neuronal toxicity. Notably, co-exposure profiles typical of certain farming practices were found to exacerbate mitochondrial dysfunction beyond single-agent effects, with the herbicide trifluralin highlighted as a potent driver of neurodegenerative changes.

Environmental Exposures and Parkinson's Disease Risk publication trend

The graph below shows the total number of articles in environmental exposures and parkinson's disease risk across all publications each year (not limited to Nature Index journals).

Technical terms

Induced pluripotent stem cell (iPSC): A reprogrammed adult cell capable of differentiating into various cell types, including neurons.

Dopaminergic neuron: A nerve cell that produces dopamine, critical for motor control and substantially lost in PD.

Mitochondrial dysfunction: Impaired energy production within the cell’s mitochondria, leading to increased oxidative stress.

Epidemiological study: Research analysing health outcomes in populations to identify associations with exposures.

Co-exposure: Simultaneous or sequential contact with multiple environmental agents, which may interact synergistically.

Neurotoxicity: The capacity of a substance to harm the structure or function of the nervous system.

References

1. A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides. Nature Communications (2023).
2. Towards improved screening of toxins for Parkinson’s risk. npj Parkinson's Disease (2023).
3. Parkinson's Disease and the Environment. Frontiers in Neurology (2019).
4. Environmental Exposures and Parkinson’s Disease. International Journal of Environmental Research and Public Health (2016).
5. Association of Cumulative Lead Exposure with Parkinson’s Disease. Environmental Health Perspectives (2010).
6. Dopamine Transporter Genetic Variants and Pesticides in Parkinson’s Disease. Environmental Health Perspectives (2009).
7. Organophosphate Pesticide Exposures, Nitric Oxide Synthase Gene Variants, and Gene–Pesticide Interactions in a Case–Control Study of Parkinson’s Disease, California (USA). Environmental Health Perspectives (2015).