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Disease-Toxicant Interactions in Parkinson’s Disease Neuropathology

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Abstract

Human disease commonly manifests as a result of complex genetic and environmental interactions. In the case of neurodegenerative diseases, such as Parkinson’s disease (PD), understanding how environmental exposures collude with genetic polymorphisms in the central nervous system to cause dysfunction is critical in order to develop better treatment strategies, therapies, and a more cohesive paradigm for future research. The intersection of genetics and the environment in disease etiology is particularly relevant in the context of their shared pathophysiological mechanisms. This review offers an integrated view of disease-toxicant interactions in PD. Particular attention is dedicated to how mutations in the genes SNCA, parkin, leucine-rich repeat kinase 2 (LRRK2) and DJ-1, as well as dysfunction of the ubiquitin proteasome system, may contribute to PD and how exposure to heavy metals, pesticides and illicit drugs may further the consequences of these mutations to exacerbate PD and PD-like disorders. Although the toxic effects induced by exposure to these environmental factors may not be the primary causes of PD, their mechanisms of action are critical for our current understanding of the neuropathologies driving PD. Elucidating how environment and genetics collude to cause pathogenesis of PD will facilitate the development of more effective treatments for the disease. Additionally, we discuss the neuroprotection exerted by estrogen and other compounds that may prevent PD and provide an overview of current treatment strategies and therapies.

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Acknowledgments

GFK was supported in part by Oberlin College Office of Foundation, Government, and Corporate Grants. RAM was supported in part by Robert Rich Student Research Grant at Oberlin College. MA was supported in part by NIEHS Grants R01ES07331, R01ES10563 and R01ES020852.

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Authors and Affiliations

  1. Department of Neuroscience, Oberlin College, 119 Woodland St., Room K232, Oberlin, OH, 44074, USA

    Gunnar F. Kwakye & Rachael A. McMinimy

  2. Departments of Molecular Pharmacology and Pediatrics, Albert Einstein College of Medicine, Forchheimer 209, 1300 Morris Park Avenue, Bronx, NY, USA

    Michael Aschner

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  1. Gunnar F. Kwakye
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  3. Michael Aschner
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Correspondence to Gunnar F. Kwakye or Michael Aschner.

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Kwakye, G.F., McMinimy, R.A. & Aschner, M. Disease-Toxicant Interactions in Parkinson’s Disease Neuropathology. Neurochem Res 42, 1772–1786 (2017). https://doi.org/10.1007/s11064-016-2052-4

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