Agrochemicals, α-synuclein, and Parkinson's disease

Mol Neurobiol. 2013 Apr;47(2):598-612. doi: 10.1007/s12035-012-8333-2. Epub 2012 Aug 30.

Abstract

Epidemiological, population-based case-control, and experimental studies at the molecular, cellular, and organism levels revealed that exposure to various environmental agents, including a number of structurally different agrochemicals, may contribute to the pathogenesis of Parkinson's disease (PD) and several other neurodegenerative disorders. The role of genetic predisposition in PD has also been increasingly acknowledged, driven by the identification of a number of disease-related genes [e.g., α-synuclein, parkin, DJ-1, ubiquitin C-terminal hydrolase isozyme L1 (UCH-L1), and nuclear receptor-related factor 1]. Therefore, the etiology of this multifactorial disease is likely to involve both genetic and environmental factors. Various neurotoxicants, including agrochemicals, have been shown to elevate the levels of α-synuclein expression in neurons and to promote aggregation of this protein in vivo. Many agrochemicals physically interact with α-synuclein and accelerate the fibrillation and aggregation rates of this protein in vitro. This review analyzes some of the aspects linking α-synuclein to PD, provides brief structural and functional descriptions of this important protein, and represents some data connecting exposure to agrochemicals with α-synuclein aggregation and PD pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Agrochemicals / chemistry
  • Agrochemicals / metabolism*
  • Agrochemicals / toxicity
  • Animals
  • Environmental Exposure / adverse effects
  • Environmental Pollutants / chemistry
  • Environmental Pollutants / metabolism*
  • Environmental Pollutants / toxicity
  • Humans
  • Parkinson Disease, Secondary / chemically induced*
  • Parkinson Disease, Secondary / etiology
  • Parkinson Disease, Secondary / metabolism*
  • alpha-Synuclein / adverse effects
  • alpha-Synuclein / metabolism*
  • alpha-Synuclein / toxicity

Substances

  • Agrochemicals
  • Environmental Pollutants
  • alpha-Synuclein