title: Oxidative toxicity in neurodegenerative diseases: role of mitochondrial dysfunction and therapeutic strategies.
abstract: Besides fluorine, oxygen is the most electronegative element with the highest reduction potential in biological systems. Metabolic pathways in mammalian cells utilize oxygen as the ultimate oxidizing agent to harvest free energy. They are very efficient, but not without risk of generating various oxygen radicals. These cells have good antioxidative defense mechanisms to neutralize these radicals and prevent oxidative stress. However, increased oxidative stress results in oxidative modifications in lipid, protein, and nucleic acids, leading to mitochondrial dysfunction and cell death. Oxidative stress and mitochondrial dysfunction have been implicated in many neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and stroke-related brain damage. Research has indicated mitochondria play a central role in cell suicide. An increase in oxidative stress causes mitochondrial dysfunction, leading to more production of reactive oxygen species and eventually mitochondrial membrane permeabilization. Once the mitochondria are destabilized, cells are destined to commit suicide. Therefore, antioxidative agents alone are not sufficient to protect neuronal loss in many neurodegenerative diseases. Combinatorial treatment with antioxidative agents could stabilize mitochondria and may be the most suitable strategy to prevent neuronal loss. This review discusses recent work related to oxidative toxicity in the central nervous system and strategies to treat neurodegenerative diseases.
authors.affiliation: Department of Chemistry & Biochemistry, University of Windsor, 277-1 Essex Hall, 401 Sunset Avenue, Windsor, ON, Canada N9B 3P4.
authors.forename: Katie
authors.initials: K
authors.lastname: Facecchia
authors.forename: Lee-Anne
authors.initials: LA
authors.lastname: Fochesato
authors.forename: Sidhartha D
authors.initials: SD
authors.lastname: Ray
authors.forename: Sidney J
authors.initials: SJ
authors.lastname: Stohs
authors.forename: Siyaram
authors.initials: S
authors.lastname: Pandey