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

• Published in: Neurobiology of disease 2006, Vol.21 (1), p.29-34
• Main Authors: Ridet, Jean-Luc, Bensadoun, Jean-Charles, Déglon, Nicole, Aebischer, Patrick, Zurn, Anne D.
• Format: Article
• Language: English
• Subjects: Animals; Anti-oxidant enzymes; Antioxidants - metabolism; Cell Line, Tumor; Disease Models, Animal; Experimental model; Gene Expression Regulation, Enzymologic; Gene therapy; Genetic Therapy - methods; Glutathione peroxidase; Glutathione Peroxidase - genetics; Lentiviral vector; Lentivirus - genetics; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neuroblastoma; Neuroprotection; Oxidative stress; Oxidopamine - toxicity; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - therapy; Parkinson's disease; Sympatholytics - toxicity; Viral vectors
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2005.06.003

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.