title: Synthetic superoxide dismutase/catalase mimetics reduce oxidative stress and prolong survival in a mouse amyotrophic lateral sclerosis model.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that causes motoneuron degeneration, paralysis and death. Mutations in Cu, Zn superoxide dismutase (SOD1) are one cause of this disease. It is widely suspected that increased reactive oxidative species (ROS) is involved in motoneuron degeneration but whether such an involvement plays a role in ALS progression in vivo is uncertain. We treated mice expressing human mutant SOD1 G93A with EUK-8 and EUK-134, two synthetic SOD/catalase mimetics that have shown efficacy in several animal models of human diseases. These treatments reduced levels of oxidative stress and prolonged survival. The results suggest that oxidative stress plays an active role in ALS and illustrate the potential for treatment strategies aimed specifically against ROS.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655, USA.
authors.forename: C
authors.initials: C
authors.lastname: Jung
authors.forename: Y
authors.initials: Y
authors.lastname: Rong
authors.forename: S
authors.initials: S
authors.lastname: Doctrow
authors.forename: M
authors.initials: M
authors.lastname: Baudry
authors.forename: B
authors.initials: B
authors.lastname: Malfroy
authors.forename: Z
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D000818:Animals; D002374:Catalase / Q000737:chemistry*; D008345:Manganese; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D016019:Survival Analysis
chemical_list: D009942:Organometallic Compounds; D008345:Manganese; D002374:Catalase; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase