Biomarkers in Duchenne Muscular Dystrophy

Lee-Gannon, Theo; Jiang, Xuan; Tassin, Tara C.; Mammen, Pradeep P.A.

doi:10.1007/s11897-022-00541-6

Cited by 6 publications

(6 citation statements)

References 88 publications

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“…We have also shown the consequences of dystrophin deficiency, as the enrichment of several important pathways, including the innate and adaptive immune system, ECM organization, protein translation, post-translational modification, programmed cell death, and cellular response to stress, was evident. Some of the detected proteins have already been mentioned in the literature, giving our results additional confirmatory status [58]. One of the examples could be the differences in the expression of various collagen isoforms.…”

Section: Discussionsupporting

confidence: 83%

Proteome Profiling of the Dystrophic mdx Mice Diaphragm

Mucha,

Myszka,

Podkalicka

et al. 2023

Biomolecules

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Mdx mice with a spontaneous mutation in exon 23 of the Dmd gene represent the most common model to investigate the pathophysiology of Duchenne muscular dystrophy (DMD). The disease, caused by the lack of functional dystrophin, is characterized by irreversible impairment of muscle functions, with the diaphragm affected earlier and more severely than other skeletal muscles. We applied a label-free (LF) method and the more thorough tandem mass tag (TMT)-based method to analyze differentially expressed proteins in the diaphragm of 6-week-old mdx mice. The comparison of both methods revealed 88 commonly changed proteins. A more in-depth analysis of the TMT-based method showed 953 significantly changed proteins, with 867 increased and 86 decreased in dystrophic animals (q-value < 0.05, fold-change threshold: 1.5). Consequently, several dysregulated processes were demonstrated, including the immune response, fibrosis, translation, and programmed cell death. Interestingly, in the dystrophic diaphragm, we found a significant decrease in the expression of enzymes generating hydrogen sulfide (H2S), suggesting that alterations in the metabolism of this gaseous mediator could modulate DMD progression, which could be a potential target for pharmacological intervention.

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Section: Discussionsupporting

confidence: 83%

Proteome Profiling of the Dystrophic mdx Mice Diaphragm

Mucha,

Myszka,

Podkalicka

et al. 2023

Biomolecules

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“…MMPs have been linked with a critical regulator of inflammation and innate immune-response regulators [ 92 ]; therefore, MMPs are being explored as a potential target as an anti-inflammatory therapy for the treatment of muscle diseases. Many MMPs are linked with inflammatory conditions in various muscle-related disorders [ 73 , 93 ]. The expression, activation, and regulation of MMP-9 have been linked to inflammatory myopathies [ 63 ].…”

Section: Function Of Mmps In Musculoskeletal Diseasesmentioning

confidence: 99%

Role of Matrix Metalloproteinases in Musculoskeletal Diseases

et al. 2022

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Musculoskeletal disorders include rheumatoid arthritis, osteoarthritis, sarcopenia, injury, stiffness, and bone loss. The prevalence of these conditions is frequent among elderly populations with significant mobility and mortality rates. This may lead to extreme discomfort and detrimental effect on the patient’s health and socioeconomic situation. Muscles, ligaments, tendons, and soft tissue are vital for body function and movement. Matrix metalloproteinases (MMPs) are regulatory proteases involved in synthesizing, degrading, and remodeling extracellular matrix (ECM) components. By modulating ECM reconstruction, cellular migration, and differentiation, MMPs preserve myofiber integrity and homeostasis. In this review, the role of MMPs in skeletal muscle function, muscle injury and repair, skeletal muscle inflammation, and muscular dystrophy and future approaches for MMP-based therapies in musculoskeletal disorders are discussed at the cellular and molecule level.

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“…Proteomic surveys of dystrophin-deficient hearts have been carried out by both top-down/gel-based proteomics and bottom-up proteomics [ 323 , 324 , 325 ]. Cardioproteomics is an established field within the systems biological multi-omics approach to determine the underlying mechanisms of heart disease [ 326 , 327 , 328 , 329 ].…”

Section: The Pathoproteomic Profiling Of Duchenne Muscular Dystrophymentioning

confidence: 99%

“…Hence, for the optimum pre-clinical testing of new therapies, the clinical evaluation of diverse patient cohorts during the various phases of clinal studies/trials, and long-term therapeutic monitoring, robust and specific biomarkers for the routine screening of the status of dystrophic patients are required [ 144 , 264 , 265 , 410 , 411 ]. Ideal protein biomarkers would be measurable in a non-invasive, or at least minimally invasive, way and be suitable for repeated sampling procedures [ 325 , 345 , 410 , 411 , 412 ].…”

Section: The Pathoproteomic Profiling Of Duchenne Muscular Dystrophymentioning

confidence: 99%

How Can Proteomics Help to Elucidate the Pathophysiological Crosstalk in Muscular Dystrophy and Associated Multi-System Dysfunction?

Dowling,

Trollet,

Negroni

et al. 2024

Proteomes

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This perspective article is concerned with the question of how proteomics, which is a core technique of systems biology that is deeply embedded in the multi-omics field of modern bioresearch, can help us better understand the molecular pathogenesis of complex diseases. As an illustrative example of a monogenetic disorder that primarily affects the neuromuscular system but is characterized by a plethora of multi-system pathophysiological alterations, the muscle-wasting disease Duchenne muscular dystrophy was examined. Recent achievements in the field of dystrophinopathy research are described with special reference to the proteome-wide complexity of neuromuscular changes and body-wide alterations/adaptations. Based on a description of the current applications of top-down versus bottom-up proteomic approaches and their technical challenges, future systems biological approaches are outlined. The envisaged holistic and integromic bioanalysis would encompass the integration of diverse omics-type studies including inter- and intra-proteomics as the core disciplines for systematic protein evaluations, with sophisticated biomolecular analyses, including physiology, molecular biology, biochemistry and histochemistry. Integrated proteomic findings promise to be instrumental in improving our detailed knowledge of pathogenic mechanisms and multi-system dysfunction, widening the available biomarker signature of dystrophinopathy for improved diagnostic/prognostic procedures, and advancing the identification of novel therapeutic targets to treat Duchenne muscular dystrophy.

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Biomarkers in Duchenne Muscular Dystrophy

Cited by 6 publications

References 88 publications

Proteome Profiling of the Dystrophic mdx Mice Diaphragm

Proteome Profiling of the Dystrophic mdx Mice Diaphragm

Role of Matrix Metalloproteinases in Musculoskeletal Diseases

How Can Proteomics Help to Elucidate the Pathophysiological Crosstalk in Muscular Dystrophy and Associated Multi-System Dysfunction?

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