LRRK2 mutations and neurotoxicant susceptibility

Exp Biol Med (Maywood). 2015 Jun;240(6):752-9. doi: 10.1177/1535370215579162. Epub 2015 Apr 16.

Abstract

Interactions between genetic and environmental factors are thought to contribute to the pathogenesis of the majority of Parkinson's disease (PD) cases. However, our understanding of these interactions is at an early stage. Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of hereditary PD. Penetrance of LRRK2 mutations is incomplete and variable, suggesting that other environmental or genetic factors may contribute to the development of the disorder. Recently, using animal models, several attempts have been made to understand if LRRK2 may mediate sensitivity to environmental neurotoxicants. Here, we critically review the most current data on how LRRK2 mutations influence neurotoxicity in PD models.

Keywords: Parkinson’s disease; gene–environment interaction; leucine-rich repeat kinase 2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease*
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Mutation*
  • Neurotoxins / toxicity*
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / genetics*
  • Parkinson Disease, Secondary / metabolism
  • Parkinson Disease, Secondary / pathology
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism

Substances

  • Neurotoxins
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases