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Commentary Open Access
Volume 3 | Issue 3 | DOI: https://doi.org/10.33696/Signaling.3.079

Oxidative DNA Damage: A Role in Altering Neuronal Function

  • 1Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
  • 2Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA
  • 3Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
  • 4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
  • 5Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA
+ Affiliations - Affiliations

Corresponding Author

Jill C. Fehrenbacher, jfehrenb@iu.edu

Received Date: July 06, 2022

Accepted Date: August 16, 2022

Abstract

A role for oxidative stress in the etiology of myriad neuropathologies is well accepted. However, the specific effects of oxidative DNA damage in the onset or promotion of neuronal dysfunction have been less studied. In our recent publication by Behrouzi et al. (Oxidative DNA Damage and Cisplatin Neurotoxicity Is Exacerbated by Inhibition of OGG1 Glycosylase Activity and APE1 Endonuclease Activity in Sensory Neurons), inhibition of enzymes that play a role in repairing oxidative DNA damage exacerbated neurotoxic effects of the chemotherapeutic agent, cisplatin. In this Commentary, we aim to expand on the contribution of oxidative DNA damage to other neuropathologies within the peripheral and central nervous systems, including irritable bowel disease, aging and Alzheimer’s disease, amyotrophic lateral sclerosis, and other neurodegenerative diseases. Consistently, clinical neuropathology and disease progression correlates with increases in oxidative DNA damage within clinical biopsies. Progress in animal models of these diseases has elucidated a causative role for oxidative DNA damage in disease progression, as dampening the DNA repair response exacerbates disease, whereas promoting DNA repair mitigates disease. Overall, this Commentary highlights the importance of expanding our studies on oxidative DNA damage in the nervous system, as enhancing oxidative DNA repair might prove to be a potential therapeutic target for the mitigation of neurodegeneration.

Keywords

Oxidative stress, Oxidative DNA damage, Base excision repair, 8-oxoguanine DNA glycosylase-1, Apurinic/apyrimidinic endonuclease/redox effector factor 1, Chemotherapy-induced peripheral neuropathy, Inflammatory bowel disease, Alzheimer’s disease, Aging, Amyotrophic lateral sclerosis

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