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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antioxidants / therapeutic use*
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Ataxia Telangiectasia / drug therapy*
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Ataxia Telangiectasia / genetics
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Ataxia Telangiectasia Mutated Proteins
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Brain / metabolism
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Catalysis
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Cell Cycle Proteins
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DNA-Binding Proteins
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Disease Models, Animal
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Fatty Acids / metabolism
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Mice
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Mice, Knockout
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Organometallic Compounds / therapeutic use*
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Oxidation-Reduction / drug effects
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Protein Serine-Threonine Kinases / genetics
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Rotarod Performance Test
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Salicylates / therapeutic use*
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Tumor Suppressor Proteins
Substances
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Antioxidants
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Cell Cycle Proteins
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DNA-Binding Proteins
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EUK-189
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Fatty Acids
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Organometallic Compounds
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Salicylates
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Tumor Suppressor Proteins
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Atm protein, mouse
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Protein Serine-Threonine Kinases