title: Treatment with a catalytic antioxidant corrects the neurobehavioral defect in ataxia-telangiectasia mice.
abstract: Ataxia-telangiectasia is caused by mutations in the ATM gene, the protein product of which is essential for effective response to double-stranded DNA breaks. Loss of ATM function explains most aspects of the disease, but not the cerebellar neurodegeneration characteristic of the disease. Mice lacking ATM provide an excellent model of the human disorder. In addition to deficient response to DNA damage, these mice exhibit oxidative stress, which we hypothesized is the cause of cerebellar dysfunction. We show that treatment with a catalytic antioxidant corrects the neurobehavioral deficit in these mice.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Browne
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Dennery
authors.forename: Susan R
authors.initials: SR
authors.lastname: Doctrow
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
authors.forename: Carrolee
authors.initials: C
authors.lastname: Barlow
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Levine
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001260:Ataxia Telangiectasia / Q000188:drug therapy* / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D001921:Brain / Q000378:metabolism; D002384:Catalysis; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009942:Organometallic Compounds / Q000627:therapeutic use*; D010084:Oxidation-Reduction / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D045442:Rotarod Performance Test; D012459:Salicylates / Q000627:therapeutic use*; D025521:Tumor Suppressor Proteins
chemical_list: D000975:Antioxidants; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C436526:EUK-189; D005227:Fatty Acids; D009942:Organometallic Compounds; D012459:Salicylates; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases