Survival motor neuron (SMN) protein in the spinal anterior horn cells of patients with sporadic amyotrophic lateral sclerosis
Survival motor neuron (SMN) protein in the spinal anterior horn cells of patients with sporadic amyotrophic lateral sclerosis
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散发性肌萎缩侧索硬化症患者脊髓前角细胞中的运动神经元（SMN）存活蛋白
DOI：
10.1016/j.brainres.2010.11.070
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发表时间：
2011
期刊：
影响因子：
2.9
通讯作者：
Oyanagi K
中科院分区：
文献类型：
--
作者：
Piao Y;Hashimoto T;Takahama S;Kakita A;Komori T;Morita T;Takahashi H;Mizutani;T;Oyanagi K
肌萎缩侧索硬化症（amyotrophiclateralsclerosis，ALS）是一种主要累及成年人上下运动神经元的致死性神经退行性疾病。关于ALS中脊髓前角细胞（AHC）变性的病理机制，已报道了在散发性ALS中存活运动神经元（SMN）基因的拷贝数异常。SMN蛋白是负责脊髓性肌萎缩症（SMA）发病机制的蛋白质，脊髓性肌萎缩症是一种常染色体隐性疾病，其特征是下运动神经元丢失和肌肉萎缩。该疾病是由SMA相关基因SMN1突变引起的SMN蛋白缺乏引起的。为了阐明SMN蛋白在sALS患者脊髓AHC变性中的作用，我们使用细胞荧光光度法检测了9例sALS患者和10例对照受试者中单个AHC细胞胞质SMN蛋白的量。结果发现：SMN蛋白在sALS患者和对照组的AHC中表达均与细胞大小有关，SMN蛋白在sALS患者和对照组的AHC中表达均与细胞大小有关，SMN蛋白在sALS患者和对照组的AHC中的单位面积表达无明显差异。这些研究结果表明：1）在sALS患者和对照中，根据细胞大小严格控制AHC细胞质中SMN蛋白的量，2）当AHC萎缩时，sALS患者的AHC中SMN蛋白的量可能减少，和3）根据它们的大小，sALS患者的AHC中SMN蛋白的减少可能是继发的而不是原发的现象。
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving mainly the upper and lower motor neurons of adult humans. With regard to the pathomechanism of spinal anterior horn cell (AHC) degeneration in ALS, copy number abnormalities of the survival motor neuron (SMN) genes have been reported in sporadic (s) ALS. SMN protein is the protein responsible for the pathogenesis of spinal muscular atrophy (SMA), an autosomal recessive disease characterized by lower motor neuron loss and muscle atrophy. The disease is caused by deficiency of SMN protein induced by mutation of one of the SMA-associated genes, SMN1. To clarify the role of SMN protein in the degeneration of spinal AHCs in sALS, we examined the amount of cytoplasmic SMN protein in individual AHCs using cytofluorophotometry in 9 patients with sALS and 10 control subjects. It was found that: 1) SMN protein was present in the cytoplasm, nucleus and nucleolus of AHCs and in the nucleus of glial cells, 2) expression of SMN protein in AHCs was significantly associated with cell size in both sALS patients and controls, 3) expression of SMN protein per unit area in AHCs was similar in sALS patients and controls. These findings suggest that: 1) the amount of SMN protein in the cytoplasm of AHCs is strictly controlled in accordance with cell size, in both sALS patients and controls, 2) the amount of SMN protein in the AHCs of sALS patients may be reduced when the AHCs are atrophic, and 3) decrease of SMN protein in the AHCs of sALS patients may be a secondary, and not primary, phenomenon according to their sizes.