Den Hartog Lily, Asakura Atsushi
Department of Neurology, Stem Cell Institute, Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Minneapolis, MN, United States.
Front Physiol. 2022 Sep 27;13:984373. doi: 10.3389/fphys.2022.984373. eCollection 2022.
This review focuses upon the implications of the Notch signaling pathway in muscular dystrophies, particularly Duchenne muscular dystrophy (DMD): a pervasive and catastrophic condition concerned with skeletal muscle degeneration. Prior work has defined the pathogenesis of DMD, and several therapeutic approaches have been undertaken in order to regenerate skeletal muscle tissue and ameliorate the phenotype. There is presently no cure for DMD, but a promising avenue for novel therapies is inducing muscle regeneration via satellite cells (muscle stem cells). One specific target using this approach is the Notch signaling pathway. The canonical Notch signaling pathway has been well-characterized and it ultimately governs cell fate decision, cell proliferation, and induction of differentiation. Additionally, inhibition of the Notch signaling pathway has been directly implicated in the deficits seen with muscular dystrophies. Here, we explore the connection between the Notch signaling pathway and DMD, as well as how Notch signaling may be targeted to improve the muscle degeneration seen in muscular dystrophies.
本综述聚焦于Notch信号通路在肌肉营养不良症,尤其是杜氏肌营养不良症(DMD)中的意义:DMD是一种普遍存在且灾难性的疾病,与骨骼肌退化有关。先前的研究已明确了DMD的发病机制,并且已经采取了几种治疗方法来再生骨骼肌组织并改善其表型。目前DMD尚无治愈方法,但一种有前景的新疗法途径是通过卫星细胞(肌肉干细胞)诱导肌肉再生。使用这种方法的一个特定靶点是Notch信号通路。经典的Notch信号通路已得到充分表征,它最终决定细胞命运、细胞增殖和诱导分化。此外,Notch信号通路的抑制与肌肉营养不良症中出现的缺陷直接相关。在此,我们探讨Notch信号通路与DMD之间的联系,以及如何靶向Notch信号以改善肌肉营养不良症中出现的肌肉退化。