Disease-Toxicant Interactions in Parkinson’s Disease Neuropathology

Gunnar F. Kwakye, Rachael A. McMinimy, Michael Aschner

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1772-1786
Number of pages15
JournalNeurochemical Research
Volume42
Issue number6
DOIs
StatePublished - Jun 1 2017

Keywords

  • Disease-toxicant interaction
  • Estrogen
  • Gene-environment interaction
  • Heavy metals
  • Illicit drugs
  • Neurodegeneration
  • Parkinson’s disease (PD)
  • Pesticides

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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