title: Oxidative stress, DNA damage, and the telomeric complex as therapeutic targets in acute neurodegeneration.
abstract: Oxidative stress has been identified as an important contributor to neurodegeneration associated with acute CNS injuries and diseases such as spinal cord injury (SCI), traumatic brain injury (TBI), and ischemic stroke. In this review, we briefly detail the damaging effects of oxidative stress (lipid peroxidation, protein oxidation, etc.) with a particular emphasis on DNA damage. Evidence for DNA damage in acute CNS injuries is presented along with its downstream effects on neuronal viability. In particular, unchecked oxidative DNA damage initiates a series of signaling events (e.g. activation of p53 and PARP-1, cell cycle re-activation) which have been shown to promote neuronal loss following CNS injury. These findings suggest that preventing DNA damage might be an effective way to promote neuronal survival and enhance neurological recovery in these conditions. Finally, we identify the telomere and telomere-associated proteins (e.g. telomerase) as novel therapeutic targets in the treatment of neurodegeneration due to their ability to modulate the neuronal response to both oxidative stress and DNA damage.
authors: Division of Neurology, Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas St., Clinical Sciences Building Room 309, Charleston, SC 29425, USA. smijo@musc.edu
authors: Joshua A
authors: JA
authors: Smith
authors: Sookyoung
authors: S
authors: Park
authors: James S
authors: JS
authors: Krause
authors: Naren L
authors: NL
authors: Banik
mesh_terms: D000818:Animals; D004249:DNA Damage; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000628:therapy*; D018384:Oxidative Stress; D016615:Telomere