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Duchenne muscular dystrophy: pathogenesis and promising therapies

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Abstract

Duchenne muscular dystrophy (DMD) is a severe, progressive, muscle-wasting disease, characterized by progressive deterioration of skeletal muscle that causes rapid loss of mobility. The failure in respiratory and cardiac muscles is the underlying cause of premature death in most patients with DMD. Mutations in the gene encoding dystrophin result in dystrophin deficiency, which is the underlying pathogenesis of DMD. Dystrophin-deficient myocytes are dysfunctional and vulnerable to injury, triggering a series of subsequent pathological changes. In this review, we detail the molecular mechanism of DMD, dystrophin deficiency-induced muscle cell damage (oxidative stress injury, dysregulated calcium homeostasis, and sarcolemma instability) and other cell damage and dysfunction (neuromuscular junction impairment and abnormal differentiation of muscle satellite). We also describe aberrant function of other cells and impaired muscle regeneration due to deterioration of the muscle microenvironment, and dystrophin deficiency-induced multiple organ dysfunction, while summarizing the recent advances in the treatment of DMD.

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Acknowledgements

I am grateful for the contribution to language help and writing assistance from Lai Xu at Nantong University during the research.

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 82072160, 32130060, 81901933, 32000725), the Major Natural Science Research Projects in Universities of Jiangsu Province (No. 20KJA310012), the Natural Science Foundation of Jiangsu Province (Nos. BK20202013, BK20201209, BK20200973), the "QingLan Project" in Jiangsu Universities, the Priority Academic Program Development of Jiangsu Higher Education Institutions, and Nantong Science and Technology Program (Nos. JC22022037, MS22022010).

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Author notes

  1. Mengyuan Chang, Yong Cai, and Zihui Gao have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Mengyuan Chang, Zihui Gao, Boya Liu, Cheng Zhang, Qianqian Cao, Yuntian Shen, Xinlei Yao & Hualin Sun

  2. Department of Neurology, Binhai County People’s Hospital, Yancheng, 224500, Jiangsu, People’s Republic of China

    Yong Cai

  3. Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Xin Chen

  4. Department of Clinical Medicine, Medical College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Weiran Yu

  5. Department of Ultrasound, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Xiaoyang Chen

  6. Research and Development Center for E-Learning, Ministry of Education, Beijing, 100816, People’s Republic of China

    Hualin Sun

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  1. Mengyuan Chang
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  11. Xiaoyang Chen
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Contributions

Conceptualization: HS, XY and XC. Methodology: MC, YC, ZG, XC, BL, CZ, WY, QC, YS. Resources: MC, YC, ZG, XC, BL, CZ, WY, QC, YS. Data curation: MC, YC, ZG, XC, BL, CZ, WY, QC, YS. Writing—original draft preparation: MC, YC, ZG, XY, XC and HS. Review and editing: MC, XY, XC and HS. Visualization: MC, YS, and HS. Supervision: HS. Project administration: HS. Funding acquisition: HS.

Corresponding authors

Correspondence to Xinlei Yao, Xiaoyang Chen or Hualin Sun.

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Chang, M., Cai, Y., Gao, Z. et al. Duchenne muscular dystrophy: pathogenesis and promising therapies. J Neurol 270, 3733–3749 (2023). https://doi.org/10.1007/s00415-023-11796-x

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