Schaaf Gerben J, Canibano-Fraile Rodrigo, van Gestel Tom J M, van der Ploeg Ans T, Pijnappel W W M Pim
Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Ann Transl Med. 2019 Jul;7(13):280. doi: 10.21037/atm.2019.04.48.
Skeletal muscle is capable of efficiently regenerating after damage in a process mediated by tissue-resident stem cells called satellite cells. This regenerative potential is often compromised under muscle-degenerative conditions. Consequently, the damage produced during degeneration is not efficiently repaired and the balance between repair and damage is lost. Here we review recent progress on the role of satellite cell-mediated repair in neuromuscular disorders with a focus on Pompe disease, an inherited metabolic myopathy caused by deficiency of the lysosomal enzyme acid alpha glucosidase (GAA). Studies performed in patient biopsies as well as in Pompe disease mouse models demonstrate that muscle regeneration activity is compromised despite progressing muscle damage. We describe disease-specific mechanisms of satellite cell dysfunction to highlight the differences between Pompe disease and muscle dystrophies. The mechanisms involved provide possible targets for therapy, such as modulation of autophagy, muscle exercise, and pharmacological modulation of satellite cell activation. Most of these approaches are still experimental, although promising in animal models, still warrant caution with respect to their safety and efficiency profile.
骨骼肌在称为卫星细胞的组织驻留干细胞介导的过程中，损伤后能够有效地再生。在肌肉退行性疾病条件下，这种再生潜力常常受到损害。因此，退变过程中产生的损伤无法得到有效修复，修复与损伤之间的平衡丧失。在此，我们综述了卫星细胞介导的修复在神经肌肉疾病中的作用的最新进展，重点关注庞贝病，这是一种由溶酶体酶酸性α-葡萄糖苷酶（GAA）缺乏引起的遗传性代谢性肌病。在患者活检以及庞贝病小鼠模型中进行的研究表明，尽管肌肉损伤不断进展，但肌肉再生活性仍受到损害。我们描述了卫星细胞功能障碍的疾病特异性机制，以突出庞贝病与肌肉营养不良之间的差异。所涉及的机制为治疗提供了可能的靶点，如自噬调节、肌肉运动以及卫星细胞激活的药理学调节。尽管这些方法在动物模型中很有前景，但大多数仍处于实验阶段，在安全性和有效性方面仍需谨慎。
