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肌肉疾病发病机制中的生物钟及其对杜氏肌营养不良症的治疗潜力。

Circadian Clock in Muscle Disease Etiology and Therapeutic Potential for Duchenne Muscular Dystrophy.

机构信息

Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes & Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.

出版信息

Int J Mol Sci. 2024 Apr 27;25(9):4767. doi: 10.3390/ijms25094767.

Abstract

Circadian clock and clock-controlled output pathways exert temporal control in diverse aspects of skeletal muscle physiology, including the maintenance of muscle mass, structure, function, and metabolism. They have emerged as significant players in understanding muscle disease etiology and potential therapeutic avenues, particularly in Duchenne muscular dystrophy (DMD). This review examines the intricate interplay between circadian rhythms and muscle physiology, highlighting how disruptions of circadian regulation may contribute to muscle pathophysiology and the specific mechanisms linking circadian clock dysregulation with DMD. Moreover, we discuss recent advancements in chronobiological research that have shed light on the circadian control of muscle function and its relevance to DMD. Understanding clock output pathways involved in muscle mass and function offers novel insights into the pathogenesis of DMD and unveils promising avenues for therapeutic interventions. We further explore potential chronotherapeutic strategies targeting the circadian clock to ameliorate muscle degeneration which may inform drug development efforts for muscular dystrophy.

摘要

生物钟和时钟控制的输出途径在骨骼生理学的多个方面发挥时间控制作用,包括维持肌肉质量、结构、功能和代谢。它们已成为理解肌肉疾病病因和潜在治疗途径的重要因素,特别是在杜氏肌营养不良症(DMD)中。本文综述了生物钟和肌肉生理学之间的复杂相互作用,强调了生物钟调节的破坏如何导致肌肉病理生理学,以及生物钟失调与 DMD 之间的具体机制。此外,我们还讨论了生物钟研究的最新进展,这些进展揭示了肌肉功能的昼夜节律控制及其与 DMD 的相关性。了解参与肌肉质量和功能的时钟输出途径为 DMD 的发病机制提供了新的见解,并为治疗干预措施开辟了有前途的途径。我们进一步探讨了针对生物钟的潜在时间治疗策略,以改善肌肉退化,这可能为肌肉营养不良症的药物开发提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be7d/11083552/f14fbd776719/ijms-25-04767-g001.jpg

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