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.
Ridet
Jean-Luc
JL
Division of Surgical Research and Gene Therapy Center, Department of Experimental Surgery, Lausanne University Medical School, CHUV, Pavillon 4, CH-1011 Lausanne, Switzerland.
Bensadoun
Jean-Charles
JC
Déglon
Nicole
N
Aebischer
Patrick
P
Zurn
Anne D
AD
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D015316:Genetic Therapy / Q000379:methods*; D005979:Glutathione Peroxidase / Q000235:genetics*; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009447:Neuroblastoma; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D013565:Sympatholytics / Q000633:toxicity; D000094765:Glutathione Peroxidase GPX1
D000975:Antioxidants; D013565:Sympatholytics; D016627:Oxidopamine; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1