Treatment with a catalytic antioxidant corrects the neurobehavioral defect in ataxia-telangiectasia mice
Treatment with a catalytic antioxidant corrects the neurobehavioral defect in ataxia-telangiectasia mice
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DOI：
10.1016/j.freeradbiomed.2004.01.003
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发表时间：
2004-04-01
影响因子：
7.4
通讯作者：
Levine, RL
中科院分区：
文献类型：
--
作者：
Browne, SE;Roberts, LJ;Levine, RL
共济失调-毛细血管扩张症是由ATM基因突变引起的，ATM基因的蛋白质产物对于有效应对双链DNA断裂至关重要。ATM功能的丧失可以解释该疾病的大部分方面，但不能解释该疾病的小脑神经变性特征。缺乏ATM的小鼠为人类疾病提供了一个很好的模型。除了对DNA损伤的反应不足外，这些小鼠还表现出氧化应激，我们假设这是小脑功能障碍的原因。我们发现，用催化抗氧化剂治疗可以纠正这些小鼠的神经行为缺陷。(C)2004年爱思唯尔公司All rights reserved.
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. (C) 2004 Elsevier Inc. All rights reserved.