TY - JOUR T1 - Lifespan Extension and Rescue of Spongiform Encephalopathy in Superoxide Dismutase 2 Nullizygous Mice Treated with Superoxide Dismutase–Catalase Mimetics JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8348 LP - 8353 DO - 10.1523/JNEUROSCI.21-21-08348.2001 VL - 21 IS - 21 AU - Simon Melov AU - Susan R. Doctrow AU - Julie A. Schneider AU - Joanna Haberson AU - Manisha Patel AU - Pinar E. Coskun AU - Karl Huffman AU - Douglas C. Wallace AU - Bernard Malfroy Y1 - 2001/11/01 UR - http://www.jneurosci.org/content/21/21/8348.abstract N2 - Superoxide is produced as a result of normal energy metabolism within the mitochondria and is scavenged by the mitochondrial form of superoxide dismutase (sod2). Mice with inactivated SOD2 (sod2 nullizygous mice) die prematurely, exhibiting several metabolic and mitochondrial defects and severe tissue pathologies, including a lethal spongiform neurodegenerative disorder (Li et al., 1995; Melov et al., 1998, 1999). We show that treatment ofsod2 nullizygous mice with synthetic superoxide dismutase (SOD)–catalase mimetics extends their lifespan by threefold, rescues the spongiform encephalopathy, and attenuates mitochondrial defects. This class of antioxidant compounds has been shown previously to extend lifespan in the nematode Caenorhabditis elegans (Melov et al., 2000). These new findings in mice suggest novel therapeutic approaches to neurodegenerative diseases associated with oxidative stress such as Friedreich ataxia, spongiform encephalopathies, and Alzheimer's and Parkinson's diseases, in which chronic oxidative damage to the brain has been implicated. ER -