Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Novel Molecular Approaches to Skeletal Muscle Disease and Disuse

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 14462

Share This Special Issue

Special Issue Editor

Dr. Marta Murgia

E-Mail Website
Guest Editor

1. Max-Planck-Institute of Biochemistry, 82152 Martinsried, Germany
2. Department of Biomedical Science, University of Padova, 35121 Padua, Italy
Interests: mass spectrometry-based proteomics; skeletal muscle; muscle disease; space medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

I am delighted to announce a call for submissions to a Special Issue of the International Journal of Molecular Sciences on “Novel Molecular Approaches to Skeletal Muscle Disease and Disuse”. Muscle-specific diseases with a variety of genetic and acquired causes, as well as aging and metabolic disorders, impair the function of skeletal muscle. This has consequences that extend far beyond muscle itself, with a systemic impact on quality of life. Exercise can be an important non-pharmacological therapeutic intervention counteracting the effects of disuse, but mechanistic knowledge of muscle physiopathology is a key step for its applicability and success. With this Special Issue, we aim at highlighting the impact of -omics technologies on the system analysis of muscle disease. We are looking for transcriptomics, proteomics, and metabolomic studies tackling different aspects of muscle disuse and therapeutic interventions. In addition, we intend to show how new molecular approaches, technologies, and disease models are channeling invaluable information that supports translational research and novel therapeutic approaches.

We encourage the submission of original research articles as well as reviews and meta-analyses of -omics data on all aspects of muscle disease and disuse. All submitted articles will undergo peer review.

Dr. Marta Murgia
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Skeletal muscle
Proteomics
Metabolomics
Transcriptomics
Exercise intervention
Systems biology
Disease models

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

15 pages, 9997 KiB

Open AccessArticle

Multi-Omics Approach to Mitochondrial DNA Damage in Human Muscle Fibers

by Matthias Elstner, Konrad Olszewski, Holger Prokisch, Thomas Klopstock and Marta Murgia

Int. J. Mol. Sci. 2021, 22(20), 11080; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011080 - 14 Oct 2021

Cited by 2 | Viewed by 1955

Abstract

Mitochondrial DNA deletions affect energy metabolism at tissue-specific and cell-specific threshold levels, but the pathophysiological mechanisms determining cell fate remain poorly understood. Chronic progressive external ophthalmoplegia (CPEO) is caused by mtDNA deletions and characterized by a mosaic distribution of muscle fibers with defective cytochrome oxidase (COX) activity, interspersed among fibers with retained functional respiratory chain. We used diagnostic histochemistry to distinguish COX-negative from COX-positive fibers in nine muscle biopsies from CPEO patients and performed laser capture microdissection (LCM) coupled to genome-wide gene expression analysis. To gain molecular insight into the pathogenesis, we applied network and pathway analysis to highlight molecular differences of the COX-positive and COX-negative fiber transcriptome. We then integrated our results with proteomics data that we previously obtained comparing COX-positive and COX-negative fiber sections from three other patients. By virtue of the combination of LCM and a multi-omics approach, we here provide a comprehensive resource to tackle the pathogenic changes leading to progressive respiratory chain deficiency and disease in mitochondrial deletion syndromes. Our data show that COX-negative fibers upregulate transcripts involved in translational elongation and protein synthesis. Furthermore, based on functional annotation analysis, we find that mitochondrial transcripts are the most enriched among those with significantly different expression between COX-positive and COX-negative fibers, indicating that our unbiased large-scale approach resolves the core of the pathogenic changes. Further enrichments include transcripts encoding LIM domain proteins, ubiquitin ligases, proteins involved in RNA turnover, and, interestingly, cell cycle arrest and cell death. These pathways may thus have a functional association to the molecular pathogenesis of the disease. Overall, the transcriptome and proteome show a low degree of correlation in CPEO patients, suggesting a relevant contribution of post-transcriptional mechanisms in shaping this disease phenotype. Full article

(This article belongs to the Special Issue Novel Molecular Approaches to Skeletal Muscle Disease and Disuse)

► Show Figures

Figure 1

19 pages, 6701 KiB

Open AccessArticle

Common Muscle Metabolic Signatures Highlight Arginine and Lysine Metabolism as Potential Therapeutic Targets to Combat Unhealthy Aging

by Janina Tokarz, Gabriele Möller, Anna Artati, Simone Huber, Anja Zeigerer, Bert Blaauw, Jerzy Adamski and Kenneth Allen Dyar

Int. J. Mol. Sci. 2021, 22(15), 7958; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22157958 - 26 Jul 2021

Cited by 9 | Viewed by 3393

Abstract

Biological aging research is expected to reveal modifiable molecular mechanisms that can be harnessed to slow or possibly reverse unhealthy trajectories. However, there is first an urgent need to define consensus molecular markers of healthy and unhealthy aging. Established aging hallmarks are all linked to metabolism, and a ‘rewired’ metabolic circuitry has been shown to accelerate or delay biological aging. To identify metabolic signatures distinguishing healthy from unhealthy aging trajectories, we performed nontargeted metabolomics on skeletal muscles from 2-month-old and 21-month-old mice, and after dietary and lifestyle interventions known to impact biological aging. We hypothesized that common metabolic signatures would highlight specific pathways and processes promoting healthy aging, while revealing the molecular underpinnings of unhealthy aging. Here, we report 50 metabolites that commonly distinguished aging trajectories in all cohorts, including 18 commonly reduced under unhealthy aging and 32 increased. We stratified these metabolites according to known relationships with various aging hallmarks and found the greatest associations with oxidative stress and nutrient sensing. Collectively, our data suggest interventions aimed at maintaining skeletal muscle arginine and lysine may be useful therapeutic strategies to minimize biological aging and maintain skeletal muscle health, function, and regenerative capacity in old age. Full article

(This article belongs to the Special Issue Novel Molecular Approaches to Skeletal Muscle Disease and Disuse)

► Show Figures

Figure 1

20 pages, 11200 KiB

Open AccessArticle

Running and Swimming Differently Adapt the BDNF/TrkB Pathway to a Slow Molecular Pattern at the NMJ

by Laia Just-Borràs, Víctor Cilleros-Mañé, Erica Hurtado, Olivier Biondi, Frédéric Charbonnier, Marta Tomàs, Neus Garcia, Josep Tomàs and Maria A. Lanuza

Int. J. Mol. Sci. 2021, 22(9), 4577; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094577 - 27 Apr 2021

Cited by 5 | Viewed by 2425

Abstract

Physical exercise improves motor control and related cognitive abilities and reinforces neuroprotective mechanisms in the nervous system. As peripheral nerves interact with skeletal muscles at the neuromuscular junction, modifications of this bidirectional communication by physical activity are positive to preserve this synapse as it increases quantal content and resistance to fatigue, acetylcholine receptors expansion, and myocytes’ fast-to-slow functional transition. Here, we provide the intermediate step between physical activity and functional and morphological changes by analyzing the molecular adaptations in the skeletal muscle of the full BDNF/TrkB downstream signaling pathway, directly involved in acetylcholine release and synapse maintenance. After 45 days of training at different intensities, the BDNF/TrkB molecular phenotype of trained muscles from male B6SJLF1/J mice undergo a fast-to-slow transition without affecting motor neuron size. We provide further knowledge to understand how exercise induces muscle molecular adaptations towards a slower phenotype, resistant to prolonged trains of stimulation or activity that can be useful as therapeutic tools. Full article

(This article belongs to the Special Issue Novel Molecular Approaches to Skeletal Muscle Disease and Disuse)

► Show Figures

Figure 1

Review

Jump to: Research

21 pages, 1737 KiB

Open AccessReview

Liquid Biopsy for Cancer Cachexia: Focus on Muscle-Derived microRNAs

by Roberta Belli, Elisabetta Ferraro, Alessio Molfino, Raffaella Carletti, Federica Tambaro, Paola Costelli and Maurizio Muscaritoli

Int. J. Mol. Sci. 2021, 22(16), 9007; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22169007 - 20 Aug 2021

Cited by 5 | Viewed by 2633

Abstract

Cancer cachexia displays a complex nature in which systemic inflammation, impaired energy metabolism, loss of muscle and adipose tissues result in unintentional body weight loss. Cachectic patients have a poor prognosis and the presence of cachexia reduces the tolerability of chemo/radio-therapy treatments and it is frequently the primary cause of death in advanced cancer patients. Early detection of this condition could make treatments more effective. However, early diagnostic biomarkers of cachexia are currently lacking. In recent years, although solid biopsy still remains the “gold standard” for diagnosis of cancer, liquid biopsy is gaining increasing interest as a source of easily accessible potential biomarkers. Moreover, the growing interest in circulating microRNAs (miRNAs), has made these molecules attractive for the diagnosis of several diseases, including cancer. Some muscle-derived circulating miRNA might play a pivotal role in the onset/progression of cancer cachexia. This topic is of great interest since circulating miRNAs might be easily detectable by means of liquid biopsies and might allow an early diagnosis of this syndrome. We here summarize the current knowledge on circulating muscular miRNAs involved in muscle atrophy, since they might represent easily accessible and promising biomarkers of cachexia. Full article

(This article belongs to the Special Issue Novel Molecular Approaches to Skeletal Muscle Disease and Disuse)

► Show Figures

Figure 1

21 pages, 2598 KiB

Open AccessReview

Phospholipids: Identification and Implication in Muscle Pathophysiology

by Rezlène Bargui, Audrey Solgadi, Bastien Prost, Mélanie Chester, Ana Ferreiro, Jérôme Piquereau and Maryline Moulin

Int. J. Mol. Sci. 2021, 22(15), 8176; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22158176 - 30 Jul 2021

Cited by 12 | Viewed by 3234

Abstract

Phospholipids (PLs) are amphiphilic molecules that were essential for life to become cellular. PLs have not only a key role in compartmentation as they are the main components of membrane, but they are also involved in cell signaling, cell metabolism, and even cell pathophysiology. Considered for a long time to simply be structural elements of membranes, phospholipids are increasingly being viewed as sensors of their environment and regulators of many metabolic processes. After presenting their main characteristics, we expose the increasing methods of PL detection and identification that help to understand their key role in life processes. Interest and importance of PL homeostasis is growing as pathogenic variants in genes involved in PL biosynthesis and/or remodeling are linked to human diseases. We here review diseases that involve deregulation of PL homeostasis and present a predominantly muscular phenotype. Full article

(This article belongs to the Special Issue Novel Molecular Approaches to Skeletal Muscle Disease and Disuse)

► Show Figures