Journal of Central Nervous System Disease · Published 2026-07-01 · DOI 10.1177/11795735261461554
Jamir Pitton Rissardo, Megan Katz, Vishnu Vardhan Byroju, Ana Letícia Fornari Caprara, Ian M. Walker
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.
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Rissardo, J., Katz, M., Byroju, V., et al. (2026). Neurodegeneration in Parkinson’s Disease: The Role of Environmental Toxins. Journal of Central Nervous System Disease. https://doi.org/10.1177/11795735261461554