Lentivirus-mediated expression of glutathione peroxidase: neuroprotection in murine models of Parkinson's disease
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.
Keywords: Animals ; Antioxidants/metabolism ; Cell Line ; Tumor ; Disease Models ; Animal ; Gene Expression Regulation ; Enzymologic ; Gene Therapy/ methods ; Glutathione Peroxidase/ genetics ; Lentivirus/ genetics ; Male ; Mice ; Mice ; Inbred C57BL ; Mice ; Transgenic ; Neuroblastoma ; Oxidopamine/toxicity ; Parkinson Disease/genetics/metabolism/ therapy ; Sympatholytics/toxicity
Division of Surgical Research and Gene Therapy Center, Department of Experimental Surgery, Lausanne University Medical School, CHUV, Pavillon 4, CH-1011 Lausanne, Switzerland.
Record created on 2007-03-09, modified on 2016-08-08