Mitochondrial network genes in the skeletal muscle of amyotrophic lateral sclerosis patients.

Mitochondrial network genes in the skeletal muscle of amyotrophic lateral sclerosis patients.
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肌萎缩性侧索硬化症患者骨骼肌中的线粒体网络基因。

DOI:
10.1371/journal.pone.0057739
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Michetti F
Michetti F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bernardini C;Censi F;Lattanzi W;Barba M;Calcagnini G;Giuliani A;Tasca G;Sabatelli M;Ricci E;Michetti F

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近年来的研究表明,肌肉退行性变可能导致和/或促进神经退行性变,在肌萎缩侧索硬化症(ALS)的发病机制和进展中起重要作用。为了验证这一假设,本研究试图利用微阵列技术和基因调控网络分析对人类ALS骨骼肌全基因组表达谱中功能相关基因进行分类。相关网络结构在患者和对照之间显著改变,表明与对照相比,患者的基因间连接增加。在ALS组中观察到的基因网络似乎反映了受影响个体中发生的肌肉稳态和代谢平衡的扰动。特别是,在ALS肌肉中观察到的网络包括基因(PRKR 1A,FOXO 1,TRIM 32,ACTN 3等),其功能将肌节完整性与线粒体氧化代谢联系起来。总的来说,本研究中使用的分析方法提供了观察基因之间更高水平相关性(即共同表达趋势)的可能性,这些基因的功能似乎在肌肉萎缩的进展过程中被异常激活。
Recent evidence suggested that muscle degeneration might lead and/or contribute to neurodegeneration, thus it possibly play a key role in the etiopathogenesis and progression of amyotrophic lateral sclerosis (ALS). To test this hypothesis, this study attempted to categorize functionally relevant genes within the genome-wide expression profile of human ALS skeletal muscle, using microarray technology and gene regulatory network analysis. The correlation network structures significantly change between patients and controls, indicating an increased inter-gene connection in patients compared to controls. The gene network observed in the ALS group seems to reflect the perturbation of muscle homeostasis and metabolic balance occurring in affected individuals. In particular, the network observed in the ALS muscles includes genes (PRKR1A, FOXO1, TRIM32, ACTN3, among others), whose functions connect the sarcomere integrity to mitochondrial oxidative metabolism. Overall, the analytical approach used in this study offer the possibility to observe higher levels of correlation (i.e. common expression trends) among genes, whose function seems to be aberrantly activated during the progression of muscle atrophy.
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