Abstract
Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants and/or a depletion of antioxidants. A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high energy oxidants (such as peroxynitrite) as mediators of secondary damage associated with spinal cord injury. Reactive oxygen species (ROS) (e.g., superoxide, peroxynitrite, hydroxyl radical and hydrogen peroxide) are all potential reactants capable of initiating DNA single strand breakage, with subsequent activation of the nuclear enzyme poly (ADP ribose) synthetase (PARS), leading to eventual severe energy depletion of the cells, and necrotic-type cell death. Moreover, Poly(ADP-ribosyl)ation is regulated by the synthesizing enzyme poly(ADP-ribose) polymerase-1 (PARP-1) and the degrading enzyme poly(ADP-ribose) glycohydrolase (PARG). Here, we review the roles of ROS, PARP-1 and PARG in spinal cord injury as well as the beneficial effect of the in vivo treatment with novel pharmacological tools (e.g. peroxynitrite decomposition catalysts, selective superoxide dismutase mimetics (SODm), PARP-1 and PARG inhibitors.
Keywords: Spinal cord injury, free radicals, PARP, PARG, GSH, peroxynitrite decomposition catalyst, catalytic antioxidant
Current Medicinal Chemistry
Title: Role of Free Radicals and Poly(ADP-Ribose)Polymerase-1 in the Development of Spinal Cord Injury: New Potential Therapeutic Targets
Volume: 15 Issue: 5
Author(s): S. Cuzzocrea and T. Genovese
Affiliation:
Keywords: Spinal cord injury, free radicals, PARP, PARG, GSH, peroxynitrite decomposition catalyst, catalytic antioxidant
Abstract: Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants and/or a depletion of antioxidants. A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high energy oxidants (such as peroxynitrite) as mediators of secondary damage associated with spinal cord injury. Reactive oxygen species (ROS) (e.g., superoxide, peroxynitrite, hydroxyl radical and hydrogen peroxide) are all potential reactants capable of initiating DNA single strand breakage, with subsequent activation of the nuclear enzyme poly (ADP ribose) synthetase (PARS), leading to eventual severe energy depletion of the cells, and necrotic-type cell death. Moreover, Poly(ADP-ribosyl)ation is regulated by the synthesizing enzyme poly(ADP-ribose) polymerase-1 (PARP-1) and the degrading enzyme poly(ADP-ribose) glycohydrolase (PARG). Here, we review the roles of ROS, PARP-1 and PARG in spinal cord injury as well as the beneficial effect of the in vivo treatment with novel pharmacological tools (e.g. peroxynitrite decomposition catalysts, selective superoxide dismutase mimetics (SODm), PARP-1 and PARG inhibitors.
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Cuzzocrea S. and Genovese T., Role of Free Radicals and Poly(ADP-Ribose)Polymerase-1 in the Development of Spinal Cord Injury: New Potential Therapeutic Targets, Current Medicinal Chemistry 2008; 15 (5) . https://dx.doi.org/10.2174/092986708783503177
DOI https://dx.doi.org/10.2174/092986708783503177 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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