Journal of Neural Transmission

, Volume 116, Issue 2, pp 151–160

DJ-1 protects against dopamine toxicity

  • Nirit Lev
  • Debby Ickowicz
  • Yael Barhum
  • Shaul Lev
  • Eldad Melamed
  • Daniel Offen
Parkinson's Disease and Allied Conditions - Original Article

DOI: 10.1007/s00702-008-0134-4

Cite this article as:
Lev, N., Ickowicz, D., Barhum, Y. et al. J Neural Transm (2009) 116: 151. doi:10.1007/s00702-008-0134-4

Abstract

Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons. Dopamine is a highly toxic compound leading to generation of reactive oxygen species (ROS). DJ-1 mutations lead to early-onset inherited PD. Here, we show that DJ-1 protects against dopamine toxicity. Dopamine-exposure led to upregulation of DJ-1. Overexpression of DJ-1 increased cell resistance to dopamine toxicity and reduced intracellular ROS. Contrary effects were achieved when DJ-1 levels were reduced by siRNA. Similarly, in vivo striatal administration of 6-hydroxydopamine led to upregulation of DJ-1. Upregulation of DJ-1 was mediated by the MAP kinases pathway through activation of ERK 1, 2 in vitro and in vivo. Hence, oxidative stress, generated by free cytoplasmic dopamine, leads to upregulation of DJ-1 through the MAP kinases pathway. This mechanism elucidates how mutations in DJ-1 prompt PD and imply that modulation of DJ-1 may serve as a novel neuroprotective modality.

Keywords

DopamineDJ-1Parkinson’s diseaseOxidative stressMAP kinases

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Nirit Lev
    • 1
  • Debby Ickowicz
    • 1
  • Yael Barhum
    • 1
  • Shaul Lev
    • 1
  • Eldad Melamed
    • 1
  • Daniel Offen
    • 1
  1. 1.Laboratory of Neuroscience, Department of Neurology, Felsenstein Medical Research Centre, Rabin Medical CentreTel Aviv UniversityPetah-TikvaIsrael