Induction of parkinsonism‐related proteins in the spinal motor neurons of transgenic mouse carrying a mutant SOD1 gene
Induction of parkinsonism‐related proteins in the spinal motor neurons of transgenic mouse carrying a mutant SOD1 gene
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DOI：
10.1002/jnr.22341
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发表时间：
2010-06
影响因子：
4.2
通讯作者：
N. Morimoto;M. Nagai;K. Miyazaki;Y. Ohta;T. Kurata;Y. Takehisa;Y. Ikeda;T. Matsuura;M. Asanuma;K. Abe
中科院分区：
文献类型：
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作者：
N. Morimoto;M. Nagai;K. Miyazaki;Y. Ohta;T. Kurata;Y. Takehisa;Y. Ikeda;T. Matsuura;M. Asanuma;K. Abe
肌萎缩侧索硬化症是一种由运动神经元选择性死亡引起的进行性致命性疾病，其中许多患者携带与改善氧化应激有关的超氧化物歧化酶 1 (SOD1) 基因突变。最近的研究表明，氧化应激和线粒体稳态破坏是肌萎缩侧索硬化症运动神经元变性和帕金森病中脑多巴胺神经元丧失的常见机制。因此，本研究调查了肌萎缩侧索硬化症 G93ASOD1 转基因小鼠模型脊髓运动神经元中家族性帕金森病相关蛋白 PINK1 和 DJ-1 的存在和变化。疾病发作后，脊髓运动神经元中的 PINK1 和 DJ-1 蛋白表达增加。 p53 的激活形式也增加并易位到脊髓运动神经元的细胞核，随后 p53 激活基因 608 (PAG608) 的表达增加。这是第一份证明 PAG608 表达增加与肌萎缩侧索硬化症模型脊髓运动神经元中磷酸化 p53 激活相关的报告。这些结果进一步证明肌萎缩侧索硬化症的脊髓运动神经元与帕金森病相关蛋白之间存在深刻的相关性。 © 2010 Wiley-Liss, Inc.
Amyotrophic lateral sclerosis is a progressive and fatal disease caused by selective death of motor neurons, and a number of these patients carry mutations in the superoxide dismutase 1 (SOD1) gene involved in ameliorating oxidative stress. Recent studies indicate that oxidative stress and disruption of mitochondrial homeostasis is a common mechanism for motor neuron degeneration in amyotrophic lateral sclerosis and the loss of midbrain dopamine neurons in Parkinson's disease. Therefore, the present study investigated the presence and alterations of familial Parkinson's disease‐related proteins, PINK1 and DJ‐1, in spinal motor neurons of G93ASOD1 transgenic mouse model of amyotrophic lateral sclerosis. Following onset of disease, PINK1 and DJ‐1 protein expression increased in the spinal motor neurons. The activated form of p53 also increased and translocated to the nuclei of spinal motor neurons, followed by increased expression of p53‐activated gene 608 (PAG608). This is the first report demonstrating that increased expression of PAG608 correlates with activation of phosphorylated p53 in spinal motor neurons of an amyotrophic lateral sclerosis model. These results provide further evidence of the profound correlations between spinal motor neurons of amyotrophic lateral sclerosis and parkinsonism‐related proteins. © 2010 Wiley‐Liss, Inc.