DJ-1 Changes in G93A-SOD1 Transgenic Mice: Implications for Oxidative Stress in ALS
DJ-1 Changes in G93A-SOD1 Transgenic Mice: Implications for Oxidative Stress in ALS
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DOI：
10.1007/s12031-008-9138-7
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发表时间：
2009-06-01
影响因子：
3.1
通讯作者：
Offen, Daniel
中科院分区：
文献类型：
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作者：
Lev, Nirit;Ickowicz, Debby;Offen, Daniel
肌萎缩侧索硬化症（ALS）是一种进行性、致死性、神经退行性疾病。ALS的病因仍然不清楚。越来越多的证据支持氧化应激和线粒体功能障碍可能与ALS发病机制有关的假设。DJ-1在氧化应激反应中起重要作用。本研究的目的是发现在ALS动物模型中是否存在DJ-1表达或DJ-1氧化亚型的变化。我们使用突变SOD 1（G93 A）转基因小鼠，一种常用的ALS动物模型。与野生型对照组相比，在SOD 1（G93 A）转基因小鼠的脑和脊髓中发现DJ-1 mRNA和蛋白水平上调，这在疾病早期阶段就很明显。此外，检测到DJ-1酸性亚型的增加，这意味着在SOD 1（G93 A）小鼠的CNS中存在更多的DJ-1氧化形式。这是第一份关于DJ-1可能参与ALS的报告。由于DJ-1具有抗氧化应激的保护作用，因此可能提示ALS的可能治疗靶点。
Amyotrophic lateral sclerosis (ALS) is a progressive, lethal, neurodegenerative disorder. The causes of ALS are still obscure. Accumulating evidence supports the hypothesis that oxidative stress and mitochondrial dysfunction can be implicated in ALS pathogenesis. DJ-1 plays an important role in the oxidative stress response. The aim of this study was to discover whether there are changes in DJ-1 expression or in DJ-1-oxidized isoforms in an animal model of ALS. We used mutant SOD1(G93A) transgenic mice, a commonly used animal model for ALS. Upregulation of DJ-1 mRNA and protein levels were identified in the brains and spinal cords of SOD1(G93A) transgenic mice as compared to wild-type controls, evident from an early disease stage. Furthermore, an increase in DJ-1 acidic isoforms was detected, implying that there are more oxidized forms of DJ-1 in the CNS of SOD1(G93A) mice. This is the first report of possible involvement of DJ-1 in ALS. Since DJ-1 has a protective role against oxidative stress, it may suggest a possible therapeutic target in ALS.