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Published on: May 12, 2013
Gene therapy in the nervous system with superoxide dismutase
Ilona Zemlyak1, Vitaliy Nimon, Sheila Brooke
1Dept. of Biological Sciences, Stanford University, Gilbert Lab, MC 5020, Stanford, CA 94305-5020, USA.
Brain Research
|April 25, 2006
Summary
Antioxidant gene therapy using CuZnSOD protected neurons from some insults but worsened others by increasing reactive oxygen species (ROS). This highlights the complexity of antioxidant gene therapy for neuroprotection.
Area of Science:
- Neuroscience
- Molecular Biology
- Gene Therapy
Background:
- Neuronal death from necrotic insults is linked to reactive oxygen species (ROS) generation.
- Antioxidant gene therapy is a potential strategy to mitigate such neuronal damage.
Purpose of the Study:
- To investigate the efficacy of antioxidant gene therapy targeting ROS accumulation in primary hippocampal cultures.
- To evaluate the protective effects of CuZnSOD gene therapy against different neurotoxic insults.
Main Methods:
- Generated a herpes simplex virus-1 amplicon vector to deliver the CuZnSOD gene.
- Overexpressed CuZnSOD in primary hippocampal cultures.
- Exposed cultures to sodium cyanide, kainic acid, or oxygen glucose deprivation (OGD) and assessed neuronal survival and ROS levels.
Main Results:
- CuZnSOD overexpression increased antioxidant enzyme activity and protected neurons against sodium cyanide-induced toxicity and lipid peroxidation.
- CuZnSOD failed to protect against OGD- or kainic acid-induced toxicity.
- CuZnSOD significantly exacerbated kainic acid-induced toxicity, hydrogen peroxide accumulation, and lipid peroxidation.
Conclusions:
- The effectiveness of antioxidant gene therapy is insult-specific.
- CuZnSOD overexpression can be detrimental under certain conditions due to an inability to detoxify excess hydrogen peroxide.
- These findings serve as a cautionary note for the clinical application of antioxidant gene therapy against necrotic insults.
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