Satoh Masahiko S, St-Pierre Guillaume, Rancourt Ann, Fillion Maude, Sato Sachiko
Laboratory of DNA Damage Responses and Bioimaging, Research Centre of CHU de Quebec and Axis of Oncology, Faculty of Medicine, Laval University, Quebec, Canada.
Glycobiology and Bioimaging Laboratory of Research Center for Infectious Diseases and Axis of Infectious and Immunological Diseases, Research Centre of CHU de Quebec, Faculty of Medicine, Laval University, Quebec, Canada.
FASEB J. 2025 Sep 30;39(18):e71013. doi: 10.1096/fj.202500196R.
N-acetylglucosamine (GlcNAc) is an endogenous compound with intracellular concentration closely linked to the biosynthesis of acetyllactosamine-rich N-linked oligosaccharides. These oligosaccharides interact with mammalian lectin galectin-3, mediating cell surface receptor dynamics as well as cell-cell and cell-extracellular matrix interactions. Our previous and recent studies suggest that GlcNAc, in conjunction with galectin-3, enhances muscle regeneration in vitro. We have also demonstrated that intraperitoneal GlcNAc administration improves muscle strength in mdx mice, a murine model of Duchenne muscular dystrophy (DMD). Here, we show that oral administration of GlcNAc significantly improves the spontaneous locomotor activity of mdx mice. Daily treatment with United States Pharmacopeia-grade GlcNAc at doses of 0.6, 1.2, 1.8, and 2.4 g/kg body weight for 35 days significantly enhanced nocturnal spontaneous locomotor activity, with the 1.2 g/kg body weight dose (equivalent to 0.144 g/kg body weight in humans) reducing damages of extensor digitorum longus muscle by nearly 50%. Although consecutive forced exercises, specifically horizontal and downhill treadmill running, reduced GlcNAc-mediated improvement, mice treated with 0.6 and 1.2 g/kg body weight still showed increased overall spontaneous locomotor activity under this condition, despite the lack of protection against repeated eccentric contraction-induced injury. These findings suggest that GlcNAc enhances overall muscle health, possibly through mechanisms other than direct protection from muscle injury. One possible contributing mechanism may involve enhanced muscle repair or regeneration, as suggested by our related in vitro myogenesis work. Notably, co-administration of GlcNAc with prednisolone, a corticosteroid commonly prescribed for DMD patients, further enhanced spontaneous locomotor improvement in mdx mice compared to prednisolone alone. These findings suggest that GlcNAc has the potential to improve the clinical status of DMD patients, either as a monotherapy or in combination with corticosteroids.
N-乙酰葡糖胺（GlcNAc）是一种内源性化合物，其细胞内浓度与富含乙酰乳糖胺的N-连接寡糖的生物合成密切相关。这些寡糖与哺乳动物凝集素半乳糖凝集素-3相互作用，介导细胞表面受体动力学以及细胞-细胞和细胞-细胞外基质相互作用。我们之前和最近的研究表明，GlcNAc与半乳糖凝集素-3共同作用可增强体外肌肉再生。我们还证明，腹腔注射GlcNAc可改善杜兴氏肌营养不良症（DMD）小鼠模型mdx小鼠的肌肉力量。在此，我们表明口服GlcNAc可显著改善mdx小鼠的自发运动活性。以0.6、1.2、1.8和2.4克/千克体重的美国药典级GlcNAc每日治疗35天，可显著增强夜间自发运动活性，其中1.2克/千克体重剂量（相当于人类0.144克/千克体重）可使趾长伸肌损伤减少近50%。尽管连续的强制运动，特别是水平和下坡跑步机跑步，会降低GlcNAc介导的改善效果，但以0.6和1.2克/千克体重治疗的小鼠在这种情况下仍表现出总体自发运动活性增加，尽管缺乏针对反复离心收缩诱导损伤的保护作用。这些发现表明，GlcNAc可能通过直接保护免受肌肉损伤以外的机制增强整体肌肉健康。一种可能的促成机制可能涉及增强肌肉修复或再生，正如我们相关的体外肌生成研究所示。值得注意的是，与单独使用泼尼松龙相比，将GlcNAc与泼尼松龙（一种常用于DMD患者的皮质类固醇）联合使用，可进一步增强mdx小鼠的自发运动改善。这些发现表明，GlcNAc有潜力作为单一疗法或与皮质类固醇联合使用来改善DMD患者的临床状况。
