Duchenne muscular dystrophy: pathogenesis and promising therapies

Chang, Mengyuan; Cai, Yong; Gao, Zihui; Chen, Xin; Liu, Boya; Zhang, Cheng; Yu, Weiran; Cao, Qianqian; Shen, Yuntian; Yao, Xin; Chen, Xiaoyang; Sun, Hualin

doi:10.1007/s00415-023-11796-x

Cited by 20 publications

(9 citation statements)

References 141 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DMD is one of the most common and severe forms of muscle atrophy caused by mutations in the DMD gene encoding different isoforms of antimyotrophic proteins [ 216 , 217 ]. DMD protein deficiency leads to intracellular Ca 2+ dysregulation, mitochondrial dysfunction and increased ROS production [ 218 ].…”

Section: Role Of Mitochondria In Muscle Atrophymentioning

confidence: 99%

Mitochondrial dysfunction: roles in skeletal muscle atrophy

Chen¹,

Ji²,

Liu³

et al. 2023

J Transl Med

Self Cite

View full text Add to dashboard Cite

Mitochondria play important roles in maintaining cellular homeostasis and skeletal muscle health, and damage to mitochondria can lead to a series of pathophysiological changes. Mitochondrial dysfunction can lead to skeletal muscle atrophy, and its molecular mechanism leading to skeletal muscle atrophy is complex. Understanding the pathogenesis of mitochondrial dysfunction is useful for the prevention and treatment of skeletal muscle atrophy, and finding drugs and methods to target and modulate mitochondrial function are urgent tasks in the prevention and treatment of skeletal muscle atrophy. In this review, we first discussed the roles of normal mitochondria in skeletal muscle. Importantly, we described the effect of mitochondrial dysfunction on skeletal muscle atrophy and the molecular mechanisms involved. Furthermore, the regulatory roles of different signaling pathways (AMPK-SIRT1-PGC-1α, IGF-1-PI3K-Akt-mTOR, FoxOs, JAK-STAT3, TGF-β-Smad2/3 and NF-κB pathways, etc.) and the roles of mitochondrial factors were investigated in mitochondrial dysfunction. Next, we analyzed the manifestations of mitochondrial dysfunction in muscle atrophy caused by different diseases. Finally, we summarized the preventive and therapeutic effects of targeted regulation of mitochondrial function on skeletal muscle atrophy, including drug therapy, exercise and diet, gene therapy, stem cell therapy and physical therapy. This review is of great significance for the holistic understanding of the important role of mitochondria in skeletal muscle, which is helpful for researchers to further understanding the molecular regulatory mechanism of skeletal muscle atrophy, and has an important inspiring role for the development of therapeutic strategies for muscle atrophy targeting mitochondria in the future.

show abstract

Section: Role Of Mitochondria In Muscle Atrophymentioning

confidence: 99%

Mitochondrial dysfunction: roles in skeletal muscle atrophy

Chen¹,

Ji²,

Liu³

et al. 2023

J Transl Med

Self Cite

View full text Add to dashboard Cite

show abstract

“… 54 The ongoing preclinical trials in canine models are supporting the treatment developments and options 55 , 56 , 57 and substantial advances have been made in a variety of treatments. 58 , 59 , 60 , 61 , 62 , 63 , 64 Defining the feline DMD variants supports the use of cats as a biomedical model in preclinical trials, like that of canine models.…”

Section: Discussionmentioning

confidence: 91%

Precision medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X‐linked muscular dystrophy in a cat

Shelton,

Tucciarone,

Guo

et al. 2024

Veterinary Internal Medicne

View full text Add to dashboard Cite

BackgroundMuscular dystrophies (MDs) are a large, heterogeneous group of degenerative muscle diseases. X‐linked dystrophin‐deficient MD in cats is the first genetically characterized cat model for a human disease and a few novel forms have been identified.Hypothesis/ObjectivesMuscular dystrophy was suspected in a young male domestic shorthair cat. Clinical, molecular, and genetic techniques could provide a definitive diagnosis.AnimalsA 1‐year‐old male domestic shorthair cat presented for progressive difficulty walking, macroglossia and dysphagia beginning at 6 months of age. The tongue was thickened, protruded with constant ptyalism, and thickening and rigidity of the neck and shoulders were observed.MethodsA complete neurological examination, baseline laboratory evaluation and biopsies of the trapezius muscle were performed with owner consent. Indirect immunofluorescence staining of muscle cryosections was performed using several monoclonal and polyclonal antibodies against dystrophy‐associated proteins. DNA was isolated for genomic analyses by whole genome sequencing and comparison to DNA variants in the 99 Lives Cat Genome Sequencing dataset.Results and Clinical ImportanceAspartate aminotransferase (687 IU/L) and creatine kinase (24 830 IU/L) activities were increased and mild hypokalemia (3.7 mmol/L) was present. Biopsy samples from the trapezius muscle confirmed a degenerative and regenerative myopathy and protein alterations identified by immunohistochemistry resulted in a diagnosis of a in dystrophin‐deficient form of X‐linked MD. A stop gain variant (c.4849C>T; p.Gln1617Ter) dystrophin was identified by genome sequencing. Precision/genomic medicine efforts for the domestic cat and in veterinary medicine support disease variant and animal model discovery and provide opportunities for targeted treatments for companion animals.

show abstract

“…Our prior studies have indicated that inflammation and oxidative stress are significant factors in the advancement of muscle atrophy [ 53 – 58 ], we speculate that the shifts in MuSCs are closely tied to the inflammation and oxidative stress elicited by disease within the muscle microenvironment. Duchenne muscular dystrophy (DMD), caused by the absence of dystrophin encoded by the DMD gene, inflicts continuous degradation and regeneration on myofibres, driving inflammation, fibrosis and ultimately, deterioration of muscle mass and functionality [ 59 , 60 ]. DMD patients' myofibres and MuSCs both express mutated dystrophin, creating anomalies in MuSC polarity, asymmetric division, and epigenetic regulation (Fig.…”

Section: Muscsmentioning

confidence: 99%

MuSCs and IPCs: roles in skeletal muscle homeostasis, aging and injury

Jiang,

Liu,

Lin

et al. 2024

Cell. Mol. Life Sci.

Self Cite

View full text Add to dashboard Cite

Skeletal muscle is a highly specialized tissue composed of myofibres that performs crucial functions in movement and metabolism. In response to external stimuli and injuries, a range of stem/progenitor cells, with muscle stem cells or satellite cells (MuSCs) being the predominant cell type, are rapidly activated to repair and regenerate skeletal muscle within weeks. Under normal conditions, MuSCs remain in a quiescent state, but become proliferative and differentiate into new myofibres in response to injury. In addition to MuSCs, some interstitial progenitor cells (IPCs) such as fibro-adipogenic progenitors (FAPs), pericytes, interstitial stem cells expressing PW1 and negative for Pax7 (PICs), muscle side population cells (SPCs), CD133-positive cells and Twist2-positive cells have been identified as playing direct or indirect roles in regenerating muscle tissue. Here, we highlight the heterogeneity, molecular markers, and functional properties of these interstitial progenitor cells, and explore the role of muscle stem/progenitor cells in skeletal muscle homeostasis, aging, and muscle-related diseases. This review provides critical insights for future stem cell therapies aimed at treating muscle-related diseases.

show abstract

Duchenne muscular dystrophy: pathogenesis and promising therapies

Cited by 20 publications

References 141 publications

Mitochondrial dysfunction: roles in skeletal muscle atrophy

Mitochondrial dysfunction: roles in skeletal muscle atrophy

Precision medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X‐linked muscular dystrophy in a cat

MuSCs and IPCs: roles in skeletal muscle homeostasis, aging and injury

Contact Info

Product

Resources

About