Wu Ruo, Song Yafeng, Wu Shiwen, Chen Yongchang
State Key Laboratory of Primate Biomedical Research & Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China.
Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, China.
Fundam Res. 2022 Jul 21;2(6):885-893. doi: 10.1016/j.fmre.2022.07.004. eCollection 2022 Nov.
Duchenne muscular dystrophy (DMD) is a serious genetic neuromuscular rare disease that is prevalent and caused by the mutation/deletion of the X-linked DMD gene that encodes dystrophin. Utrophin is a dystrophin homologous protein on human chromosome 6. Dystrophin and utrophin are highly homologous. They can recruit many dystrophin-glycoprotein complex (DGC)-related proteins and co-localize at the sarcolemma in the early stage of human embryonic development. Moreover, utrophin is overexpressed naturally at the mature myofiber sarcolemma in DMD patients. Therefore, utrophin is considered the most promising homologous protein to replace dystrophin. This review summarizes various modulating drugs and gene therapy approaches for utrophin replacement. As a universal method to treat DMD disease, utrophin has a promising therapeutic prospect and deserves further investigation.
杜氏肌营养不良症(DMD)是一种严重的遗传性神经肌肉罕见疾病,普遍存在,由编码抗肌萎缩蛋白的X连锁DMD基因突变/缺失引起。促肌萎缩蛋白是人类6号染色体上的一种抗肌萎缩蛋白同源蛋白。抗肌萎缩蛋白和促肌萎缩蛋白高度同源。它们可以募集许多与抗肌萎缩蛋白-糖蛋白复合物(DGC)相关的蛋白质,并在人类胚胎发育早期共定位于肌膜。此外,促肌萎缩蛋白在DMD患者成熟的肌纤维肌膜上自然过度表达。因此,促肌萎缩蛋白被认为是替代抗肌萎缩蛋白最有前景的同源蛋白。本综述总结了用于促肌萎缩蛋白替代的各种调节药物和基因治疗方法。作为治疗DMD疾病的通用方法,促肌萎缩蛋白具有广阔的治疗前景,值得进一步研究。