Gandhi Shivam, Sweeney Gary, Perry Christopher G R
School of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, ON M3J 1P3, Canada.
Department of Biology and Muscle Health Research Centre, York University, Toronto, ON M3J 1P3, Canada.
Biomedicines. 2024 Jun 25;12(7):1407. doi: 10.3390/biomedicines12071407.
Duchenne muscular dystrophy (DMD) is caused by genetic mutations in the cytoskeletal-sarcolemmal anchor protein dystrophin. Repeated cycles of sarcolemmal tearing and repair lead to a variety of secondary cellular and physiological stressors that are thought to contribute to weakness, atrophy, and fibrosis. Collectively, these stressors can contribute to a pro-inflammatory milieu in locomotor, cardiac, and respiratory muscles. Given the many unwanted side effects that accompany current anti-inflammatory steroid-based approaches for treating DMD (e.g., glucocorticoids), there is a need to develop new therapies that address inflammation and other cellular dysfunctions. Adiponectin receptor (AdipoR) agonists, which stimulate AdipoR1 and R2 isoforms on various cell types, have emerged as therapeutic candidates for DMD due to their anti-inflammatory, anti-fibrotic, and pro-myogenic properties in pre-clinical human and rodent DMD models. Although these molecules represent a new direction for therapeutic intervention, the mechanisms through which they elicit their beneficial effects are not yet fully understood, and DMD-specific data is limited. The overarching goal of this review is to investigate how adiponectin signaling may ameliorate pathology associated with dystrophin deficiency through inflammatory-dependent and -independent mechanisms and to determine if current data supports their future progression to clinical trials.
杜兴氏肌营养不良症（DMD）由细胞骨架-肌膜锚定蛋白抗肌萎缩蛋白的基因突变引起。肌膜反复撕裂和修复的循环导致多种继发性细胞和生理应激源，这些应激源被认为会导致肌肉无力、萎缩和纤维化。总体而言，这些应激源可导致运动、心脏和呼吸肌出现促炎环境。鉴于目前基于抗炎类固醇的DMD治疗方法存在许多不良副作用（如糖皮质激素），因此需要开发新的疗法来解决炎症和其他细胞功能障碍问题。脂联素受体（AdipoR）激动剂可刺激多种细胞类型上的AdipoR1和R2亚型，由于其在临床前人类和啮齿动物DMD模型中具有抗炎、抗纤维化和促肌生成特性，已成为DMD的治疗候选药物。尽管这些分子代表了治疗干预的新方向，但其产生有益作用的机制尚未完全明确，且DMD特异性数据有限。本综述的总体目标是研究脂联素信号传导如何通过炎症依赖性和非依赖性机制改善与抗肌萎缩蛋白缺乏相关的病理状况，并确定当前数据是否支持其未来进入临床试验。
