Article type: Literature Review
Article title: Neurodegeneration in Parkinson’s Disease: The Role of Environmental Toxins
Journal: Journal of Central Nervous System Disease
Year: 2026
Authors: Jamir Pitton Rissardo, Megan Katz, Vishnu Vardhan Byroju, Ana Letícia Fornari Caprara, and Ian M. Walker
E-mail: jamirrissardo@gmail.com
ABSTRACT
Parkinson’s disease (PD) is a rapidly growing global health challenge, with prevalence projected to reach 13–14 million cases by 2040. While aging and improved diagnostic awareness partly explain this trend, mounting evidence implicates environmental factors as critical contributors. This review synthesizes current literature on exposures such as pesticides, solvents, heavy metals, air pollutants, and infectious agents, emphasizing their mechanistic links to neurodegeneration. These factors interact with genetic susceptibility and aging, supporting the “multiple-hit” hypothesis, which posits that PD arises from cumulative insults rather than a single cause. Mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired protein clearance emerge as convergent pathways underlying dopaminergic vulnerability. Recent findings highlight viral infections—particularly SARS-CoV-2—as potential triggers or amplifiers of PD pathogenesis, raising concerns about long-term neurological sequelae following pandemics. Beyond individual toxins, the exposome concept underscores the lifelong interplay of physical, chemical, and social exposures in shaping disease risk. Climate-related changes, including increased air pollution and wildfire frequency, further compound these risks, suggesting a systemic dimension to PD etiology. Understanding these complex interactions is essential for developing preventive strategies, refining experimental models, and informing public health policies aimed at mitigating environmental contributions to neurodegeneration. This multifactorial perspective offers a foundation for future research targeting modifiable risk factors and resilience mechanisms in PD.
Keywords: Parkinson’s disease, neurodegeneration, environmental toxins, pesticides, air pollution, heavy metals, solvents, multiple-hithypothesis, SARS-CoV-2, exposome
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DOI
Citation
Pitton Rissardo J, Katz M, Byroju VV, Fornari Caprara AL, Walker IM. Neurodegeneration in Parkinson’s Disease: The Role of Environmental Toxins. Journal of Central Nervous System Disease. 2026;18. doi:10.1177/11795735261461554.
Figure 1. Likelihood of diagnosing Parkinson’s Disease (PD). The probability of a PD diagnosis increases as the cumulative burden of risk factors rises. Key contributors include aging, chronic inflammation, and exposure to environmental toxins and pollutants. These factors interact with genetic susceptibility—particularly high-penetrance mutations—to elevate disease risk. The synergistic effect of these elements underscores the multifactorial nature of PD pathogenesis.
Figure 2. Role of exposome in Parkinson’s Disease. Exposure to environmental factors through an individual’s life-time plays a role in pathogenesis of Parkinson’s disease. (A) Heavy metals (Iron, Zinc, Mercury, Lead, Copper) exposure through paint, tools and drinking water. (B) Air pollution and environmental toxins containing PM2.5, NO2, O3 and other particles. (C) Pesticide and fungicide exposure to 2,4-dichlorodiphenyldichloroethylene, Rotenone, diquat, paraquat and others. (D) Helicobacter pylori infection and other gut microbiomes exert influence. (E) Exercise and physical activity. (F) Exposure to nicotine, intravenous drugs and toxins such as MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). (G) Diet and understanding of macro and micronutrients.
Table 1. Environmental and Biological Risk Factors Associated With Parkinson’s Disease.
Table 2. Toxic Models of Parkinson’s Disease.