Carr Stephanie J, Zahedi René P, Lochmüller Hanns, Roos Andreas
John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Leibniz-Institut für Analytische Wissenschaften, ISAS e.V., Dortmund, Germany.
Proteomics Clin Appl. 2018 Mar;12(2). doi: 10.1002/prca.201700071. Epub 2017 Jul 13.
Duchenne muscular dystrophy (DMD) is a genetic muscle wasting condition with limited treatment options available and is caused by the lack of dystrophin. However, pathophysiology of different tissues is variable showing different histological and molecular signatures. Recently, a number of studies have employed gel-free proteomic approaches to unveil the molecular pathophysiology in terms of tissue-specific proteome changes in dystrophin deficiency. The authors analyzed studies in models of dystrophin deficiency and patients both from the published literature. The authors created a database containing all of the significantly differentially expressed proteins. By the integration of data from nine studies, the authors have identified 31 proteins which are commonly affected in different tissues by dystrophin deficiency. These proteins represent pathways involved in the maintenance of the actin cytoskeleton and those involved in cellular energy metabolism among others. Also represented is glyceraldehyde-3-phosphate dehydrogenase (GAPDH), often used as a loading control in protein assays, it appears to be highly variable, and should be replaced by other controls. The same intersection of data was performed using studies of the blood and urine of Duchenne muscular dystrophy patients and/or animal models and identified 33 proteins that are commonly differentially expressed. These proteins may themselves be novel therapeutic targets biomarkers that could monitor disease progression.
杜兴氏肌肉营养不良症（DMD）是一种遗传性肌肉萎缩疾病，治疗选择有限，由肌营养不良蛋白缺乏引起。然而，不同组织的病理生理学各不相同，表现出不同的组织学和分子特征。最近，一些研究采用了无凝胶蛋白质组学方法，从肌营养不良蛋白缺乏导致的组织特异性蛋白质组变化方面揭示分子病理生理学。作者分析了已发表文献中关于肌营养不良蛋白缺乏模型和患者的研究。作者创建了一个包含所有显著差异表达蛋白质的数据库。通过整合九项研究的数据，作者确定了31种在不同组织中受肌营养不良蛋白缺乏共同影响的蛋白质。这些蛋白质代表了参与肌动蛋白细胞骨架维持的途径以及参与细胞能量代谢等的途径。同样被提及的还有甘油醛-3-磷酸脱氢酶（GAPDH），它常被用作蛋白质检测中的上样对照，但其表达似乎高度可变，应该用其他对照取代。使用杜兴氏肌肉营养不良症患者和/或动物模型的血液和尿液研究进行了相同的数据交叉分析，确定了33种共同差异表达的蛋白质。这些蛋白质本身可能是新型治疗靶点生物标志物，可用于监测疾病进展。
