FUS is not dysregulated by the spinal bulbar muscular atrophy androgen receptor polyglutamine repeat expansion
FUS is not dysregulated by the spinal bulbar muscular atrophy androgen receptor polyglutamine repeat expansion
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DOI：
10.1016/j.neurobiolaging.2012.09.008
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发表时间：
2013-05-01
影响因子：
4.2
通讯作者：
Greensmith, Linda
中科院分区：
文献类型：
--
作者：
Fratta, Pietro;Malik, Bilal;Greensmith, Linda
脊髓延髓肌萎缩症（SBMA）和肌萎缩侧索硬化症是两种不同形式的运动神经元疾病，具有不同的遗传原因，病理和临床过程。然而，这两种疾病的特征在于下运动神经元的进行性丧失和动物模型中对生长因子的类似保护性反应，因此提高了最终致病级联重叠的可能性。FUS基因突变和融合肉瘤（FUS）蛋白病理学现已在一些肌萎缩侧索硬化症病例中被确定，而雄激素受体基因的CAG扩增已知会导致SBMA。最近，多条证据表明FUS是雄激素受体的主要靶点，表明FUS在SBMA运动神经元中可能失调。我们已经研究了这种可能性，通过使用一个完善的SBMA小鼠模型和我们的分析，原代运动神经元文化，脊髓，和显微解剖的运动神经元显示没有证据FUS失调。(C)2013 Elsevier Inc. All rights reserved.
Spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis are two distinct forms of motor neuron disease with different genetic causes, pathology, and clinical course. However, both disorders are characterized by the progressive loss of lower motor neurons and by a similar protective response to growth factors in animal models, therefore raising the possibility of an overlap in the final pathogenic cascade. Mutations in the FUS gene and fused in sarcoma (FUS) protein pathology have now been identified in some amyotrophic lateral sclerosis cases, while a CAG expansion in the androgen receptor gene is known to cause SBMA. Recently, multiple lines of evidence have identified FUS as a major target of the androgen receptor, suggesting that FUS could be dysregulated in SBMA motor neurons. We have investigated this possibility by using a well-established mouse model of SBMA and our analysis of primary motor neuron cultures, spinal cords, and microdissected motor neurons show no evidence for FUS dysregulation. (C) 2013 Elsevier Inc. All rights reserved.