Lentivirus-mediated expression of glutathione peroxidase: neuroprotection in murine models of Parkinson's disease

Neurobiol Dis. 2006 Jan;21(1):29-34. doi: 10.1016/j.nbd.2005.06.003. Epub 2005 Jul 14.

Abstract

Reactive oxygen species are considered to contribute to the pathogenesis of Parkinson's disease (PD). In order to study viral vector-mediated overexpression of the antioxidant enzyme glutathione peroxidase (GPX) as a potential neuroprotective approach in both an in vitro and in vivo model of PD, we have developed a lentiviral vector carrying the human GPX1 gene. Neuroblastoma cells infected with this vector showed a 2-fold increase in GPX activity compared to cells infected with a control vector. In addition, overexpression of GPX protected 83.0 +/- 14.2% of these cells against 6-hydroxydopamine (6-OHDA)-induced toxicity, while only 22.9 +/- 4.6% of the cells infected with a control vector survived. Furthermore, lentivirus-mediated expression of GPX1 in nigral dopaminergic neurons in vivo prior to intrastriatal injection of 6-OHDA led to a small, but significant protection of these cells against drug-induced toxicity. These results indicate that antioxidative gene therapy strategies may be relevant for PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Cell Line, Tumor
  • Disease Models, Animal
  • Gene Expression Regulation, Enzymologic*
  • Genetic Therapy / methods*
  • Glutathione Peroxidase / genetics*
  • Lentivirus / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuroblastoma
  • Oxidopamine / toxicity
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Parkinson Disease / therapy*
  • Sympatholytics / toxicity

Substances

  • Antioxidants
  • Sympatholytics
  • Oxidopamine
  • glutathione peroxidase GPX1
  • Glutathione Peroxidase