Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis
Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis
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DOI：
10.1002/ana.20379
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发表时间：
2005-02-01
影响因子：
11.2
通讯作者：
Sobue, G
中科院分区：
文献类型：
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作者：
Jiang, YM;Yamamoto, M;Sobue, G
散发性肌萎缩侧索硬化症（ALS）的发病机制尚不清楚。使用微阵列技术结合激光捕获显微切割，从散发性ALS尸检患者中分离的退化脊髓运动神经元的基因表达谱进行了研究。通过实时逆转录聚合酶链反应和原位杂交定量评估基因表达。脊髓运动神经元显示出与整个脊髓腹角不同的基因表达谱。在运动神经元中，3%的基因表达下调，1%的基因表达上调。下调的基因包括与细胞骨架/轴突运输、转录和细胞表面抗原/受体相关的基因，如dynactin、微管相关蛋白和早期生长反应3（EGFR 3）。相反，细胞死亡相关基因大多上调。细胞死亡途径的启动子、死亡受体5、细胞周期蛋白A1和C以及半胱天冬酶-1、-3和-9被上调，而细胞死亡抑制剂、乙酰辅酶A转运蛋白和NF-κ B也被上调。此外，神经保护性神经营养因子，如睫状神经营养因子（CNTF），肝细胞生长因子（HGF），和胶质细胞源性神经营养因子上调。然而，与炎症相关的基因，如那些属于细胞因子家族的基因，在运动神经元或腹角中没有显著上调。散发性ALS中运动神经元特异性基因表达谱可以提供导致神经变性和神经元死亡的基因的直接信息，并有助于开发新的治疗策略。
The causative pathomechanism of sporadic amyotrophic lateral sclerosis (ALS) is not clearly understood. Using microarray technology combined with laser-captured microdissection, gene expression profiles of degenerating spinal motor neurons isolated from autopsied patients with sporadic ALS were examined. Gene expression was quantitatively assessed by real-time reverse transcription polymerase chain reaction and in situ hybridization. Spinal motor neurons showed a distinct gene expression profile from the whole spinal ventral horn. Three percent of genes examined were downregulated, and 1% were upregulated in motor neurons. Downregulated genes included those associated with cytoskeleton/axonal transport, transcription, and cell surface antigens/receptors, such as dynactin, microtubule-associated proteins, and early growth response 3 (EGR3). In contrast, cell death-associated genes were mostly upregulated. Promoters for cell death pathway, death receptor 5, cyclins A1 and C, and caspases-1, -3, and -9, were upregulated, whereas cell death inhibitors, acetyl-CoA transporter, and NF-kappaB were also upregulated. Moreover, neuroprotective neurotrophic factors such as ciliary neurotrophic factor (CNTF), Hepatocyte growth factor (HGF), and glial cell line-derived neurotrophic factor were upregulated. Inflammation-related genes, such as those belonging to the cytokine family, were not, however, significantly upregulated in either motor neurons or ventral horns. The motor neuron-specific gene expression profile in sporadic ALS can provide direct information on the genes leading to neurodegeneration and neuronal death and are helpful for developing new therapeutic strategies.