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

Autor: Jean-Luc Ridet, Jean-Charles Bensadoun, Nicole Déglon, Patrick Aebischer, Anne D. Zurn
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Zdroj: Neurobiology of Disease, Vol 21, Iss 1, Pp 29-34 (2006)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2005.06.003
Popis: 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.
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