Utrophin is an autosomal paralogue of dystrophin, a protein whose deficit causes Duchenne and Becker muscular dystrophies (DMD/BMD). Utrophin is naturally overexpressed at the sarcolemma of mature dystrophin-deficient fibres in DMD and BMD patients as well as in the mdx Duchenne mouse model. Dystrophin and utrophin can co-localise in human foetal muscle, in the dystrophin-competent fibres from DMD/BMD carriers, and revertant fibre clusters in biopsies from DMD patients. These findings suggest that utrophin overexpression could act as a surrogate, compensating for the lack of dystrophin, and, as such, it could be used in combination with dystrophin restoration therapies. Different strategies to overexpress utrophin are currently under investigation. In recent years, many compounds have been reported to modulate utrophin expression efficiently in preclinical studies and ameliorate the dystrophic phenotype in animal models of the disease. In this manuscript, we discuss the current knowledge on utrophin protein and the different mechanisms that modulate its expression in skeletal muscle. We also include a comprehensive review of compounds proposed as utrophin regulators and, as such, potential therapeutic candidates for these muscular dystrophies.

中文翻译：

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Utrophin 调节剂药物作为 Duchenne 和 Becker 肌营养不良症的潜在疗法

Utrophin 是肌营养不良蛋白的常染色体旁系同源物，肌营养不良蛋白的缺乏会导致 Duchenne 和 Becker 肌营养不良症 (DMD/BMD)。Utrophin 在 DMD 和 BMD 患者以及mdx中成熟的肌营养不良蛋白缺陷纤维的肌膜自然过表达杜氏小鼠模型。Dystrophin 和 utrophin 可以共同定位于人类胎儿肌肉、来自 DMD/BMD 携带者的抗肌萎缩蛋白感受态纤维中，以及来自 DMD 患者的活检组织中的回复性纤维簇中。这些发现表明，utrophin 过表达可以作为替代物，弥补肌营养不良蛋白的缺乏，因此，它可以与肌营养不良蛋白恢复疗法联合使用。目前正在研究过表达 utrophin 的不同策略。近年来，据报道，许多化合物在临床前研究中有效调节 utrophin 表达，并改善该疾病动物模型中的营养不良表型。在这份手稿中，我们讨论了目前关于 utrophin 蛋白的知识以及调节其在骨骼肌中表达的不同机制。