Ridet Jean-Luc, Bensadoun Jean-Charles, Déglon Nicole, Aebischer Patrick, Zurn Anne D
Division of Surgical Research and Gene Therapy Center, Department of Experimental Surgery, Lausanne University Medical School, CHUV, Pavillon 4, CH-1011 Lausanne, Switzerland.
Neurobiol Dis. 2006 Jan;21(1):29-34. doi: 10.1016/j.nbd.2005.06.003. Epub 2005 Jul 14.
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.
活性氧被认为与帕金森病（PD）的发病机制有关。为了研究病毒载体介导的抗氧化酶谷胱甘肽过氧化物酶（GPX）过表达作为PD体外和体内模型中的一种潜在神经保护方法，我们构建了一种携带人GPX1基因的慢病毒载体。与感染对照载体的细胞相比，感染该载体的神经母细胞瘤细胞的GPX活性增加了2倍。此外，GPX的过表达保护了83.0±14.2%的这些细胞免受6-羟基多巴胺（6-OHDA）诱导的毒性，而感染对照载体的细胞中只有22.9±4.6%存活。此外，在脑内注射6-OHDA之前，慢病毒介导的GPX1在体内黑质多巴胺能神经元中的表达对这些细胞免受药物诱导的毒性产生了轻微但显著的保护作用。这些结果表明抗氧化基因治疗策略可能与PD相关。
