title: SOD2 in mitochondrial dysfunction and neurodegeneration.
abstract: The brain is a highly metabolically active tissue that critically relies on oxidative phosphorylation as a means for maintaining energy. One result of this process is the production of potentially damaging radicals such as the superoxide anion (O2(-)). Superoxide has the capacity to damage components of the electron transport chain and other cellular constituents. Eukaryotic systems have evolved defenses against such damaging moieties, the chief member of which is superoxide dismutase (SOD2), an enzyme that efficiently converts superoxide to the less reactive hydrogen peroxide (H2O2), which can freely diffuse across the mitochondrial membrane. Loss of SOD2 activity can result in numerous pathological phenotypes in metabolically active tissues, particularly within the central nervous system. We review SOD2's potential involvement in the progression of neurodegenerative diseases such as stroke and Alzheimer and Parkinson diseases, as well as its potential role in "normal" age-related cognitive decline. We also examine in vivo models of endogenous oxidative damage based upon the loss of SOD2 and associated neurological phenotypes in relation to human neurodegenerative disorders.
authors.affiliation: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Flynn
authors.affiliation: Buck Institute for Research on Aging, Novato, CA 94945, USA. Electronic address: SMelov@buckinstitute.org.
authors.forename: Simon
authors.initials: S
authors.lastname: Melov
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D013481:Superoxides; D000099156:Superoxide Dismutase 2
keywords: Aging; Free radicals; Mitochondria; Neurodegeneration; Oxidative stress; Superoxide dismutase