Journal
PHARMACOLOGY & THERAPEUTICS
Volume 142, Issue 2, Pages 206-230Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2013.12.007
Keywords
Antioxidant gene therapy; Brain ischemia; Neurodegenerative disorders; Oxidative stress; Virus-mediated gene delivery; ROS
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Funding
- National Institutes of Health, Centers of Biomedical Research Excellence (COBRE) [P20RR17675]
- Interdisciplinary Grant from the Research Council
- Life Sciences Grant Program of the University of Nebraska-Lincoln
- Scientist Development Grant of the American Heart Association [12SDG12090015]
- CONACYT-Mexico [104316]
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Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated in mitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. This work reviews the evidence demonstrating the ability of genetically encoded antioxidant systems to selectively counteract neuronal cell loss in neurodegenerative diseases and ischemic brain damage. Because gene therapy approaches to treat inherited and acquired disorders offer many unique advantages over conventional therapeutic approaches, we discussed basic research/clinical evidence and the potential of virus-mediated gene delivery techniques for antioxidant gene therapy. (C) 2013 Elsevier Inc All rights reserved.
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