TY - JOUR A2 - Khan, M. Firoze AU - Facecchia, Katie AU - Fochesato, Lee-Anne AU - Ray, Sidhartha D. AU - Stohs, Sidney J. AU - Pandey, Siyaram PY - 2011 DA - 2011/07/14 TI - Oxidative Toxicity in Neurodegenerative Diseases: Role of Mitochondrial Dysfunction and Therapeutic Strategies SP - 683728 VL - 2011 AB - Besides fluorine, oxygen is the most electronegative element with thehighest reduction potential in biological systems. Metabolic pathways inmammalian cells utilize oxygen as the ultimate oxidizing agent to harvest freeenergy. They are very efficient, but not without risk of generating various oxygenradicals. These cells have good antioxidative defense mechanisms to neutralizethese radicals and prevent oxidative stress. However, increased oxidative stressresults in oxidative modifications in lipid, protein, and nucleic acids, leading tomitochondrial dysfunction and cell death. Oxidative stress and mitochondrialdysfunction have been implicated in many neurodegenerative disorders includingAlzheimer's disease, Parkinson's disease, and stroke-related brain damage. Research has indicated mitochondria play a central role in cell suicide. Anincrease in oxidative stress causes mitochondrial dysfunction, leading to moreproduction of reactive oxygen species and eventually mitochondrial membranepermeabilization. Once the mitochondria are destabilized, cells are destined tocommit suicide. Therefore, antioxidative agents alone are not sufficient to protectneuronal loss in many neurodegenerative diseases. Combinatorial treatment withantioxidative agents could stabilize mitochondria and may be the most suitablestrategy to prevent neuronal loss. This review discusses recent work related tooxidative toxicity in the central nervous system and strategies to treatneurodegenerative diseases. SN - 1687-8191 UR - https://doi.org/10.1155/2011/683728 DO - 10.1155/2011/683728 JF - Journal of Toxicology PB - Hindawi Publishing Corporation KW - ER -