Mice lacking alpha-synuclein are resistant to mitochondrial toxins
Mice lacking alpha-synuclein are resistant to mitochondrial toxins
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DOI：
10.1016/j.nbd.2005.08.018
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发表时间：
2006-03-01
影响因子：
6.1
通讯作者：
Beal, MF
中科院分区：
文献类型：
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作者：
Klivenyi, P;Siwek, D;Beal, MF
α-突触核蛋白功能异常与帕金森病（PD）的发病机制有关。我们发现α-突触核蛋白缺陷小鼠对MPTP诱导的多巴胺能神经元变性具有抵抗力。对于纹状体中多巴胺和黑质中多巴胺转运蛋白（DAT）免疫反应性神经元的损失，存在剂量依赖性保护作用。这些影响不是由于MPTP处理的改变。我们发现α-突触核蛋白缺陷小鼠也对丙二酸和3-硝基丙酸（3-NP）神经毒性具有抗性。在施用3-NP后，α-突触核蛋白缺陷小鼠中活性氧的产生减少。这些发现暗示α-突触核蛋白作为氧化损伤的调节剂，其与MPTP和其他线粒体毒素产生的神经元死亡有关。(C)2005年爱思唯尔公司All rights reserved.
Abnormalities in the function of alpha-synuclein are implicated in the pathogenesis of Parkinson's disease (PD). We found that alpha-synuclein-deficient mice are resistant to MPTP-induced degeneration of dopaminergic neurons. There was dose-dependent protection against loss of both dopamine in the striatum and dopamine transporter (DAT) immunoreactive neurons in the substantia nigra. These effects were not due to alterations in MPTP processing. We found that alpha-synuclein-deficient mice are also resistant to both malonate and 3-nitropropionic acid (3-NP) neurotoxicity. There was reduced generation of reactive oxygen species in alpha-synuclein-deficient mice following administration of 3-NP. These findings implicate alpha-synuclein as a modulator of oxidative damage, which has been implicated in neuronal death produced by MPTP and other mitochondrial toxins. (C) 2005 Elsevier Inc. All rights reserved.