The Role of Autophagy in Skeletal Muscle Diseases

Skeletal muscle is the most abundant type of tissue in human body, being involved in diverse activities and maintaining a finely tuned metabolic balance. Autophagy, characterized by the autophagosome–lysosome system with the involvement of evolutionarily conserved autophagy-related genes, is an important catabolic process and plays an essential role in energy generation and consumption, as well as substance turnover processes in skeletal muscles. Autophagy in skeletal muscles is finely tuned under the tight regulation of diverse signaling pathways, and the autophagy pathway has cross-talk with other pathways to form feedback loops under physiological conditions and metabolic stress. Altered autophagy activity characterized by either increased formation of autophagosomes or inhibition of lysosome-autophagosome fusion can lead to pathological cascades, and mutations in autophagy genes and deregulation of autophagy pathways have been identified as one of the major causes for a variety of skeleton muscle disorders. The advancement of multi-omics techniques enables further understanding of the molecular and biochemical mechanisms underlying the role of autophagy in skeletal muscle disorders, which may yield novel therapeutic targets for these disorders.

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Emerging role of MyomiRs as Biomarkers and Therapeutic Targets in Skeletal Muscle Diseases

AJP Cell Physiology ◽

10.1152/ajpcell.00057.2021 ◽

2021 ◽

Author(s):

Sukanya Srivastava ◽

Richa Rathor ◽

Som Nath Singh ◽

Geetha Suryakumar

Keyword(s):

Skeletal Muscle ◽

Biological Fluids ◽

Muscle Disorders ◽

Muscle Diseases ◽

Potential Biomarker ◽

Skeletal Muscle Loss ◽

Muscle Health ◽

Diseased State ◽

Skeletal Muscle Disorders

Several chronic diseases lead to skeletal muscle loss and a decline in physical performance. MicroRNAs (miRNA) are small, non-coding RNAs, which has exhibited its role in the development and diseased state of the skeletal muscle. miRNA regulates gene expression by binding to the 3' untranslated region of its target mRNA. Due to the robust stability in biological fluids, miRNAs are ideal candidate as biomarker. These miRNAs provide a novel avenue in strengthening our awareness and knowledge about the factors governing skeletal muscle functions such as, development, growth, metabolism, differentiation and cell proliferation. It also helps in understanding the therapeutic strategies in improving or conserving skeletal muscle health. This review outlines the evidence regarding the present knowledge on the role miRNA as a potential biomarker in skeletal muscle diseases and their exploration might be a unique and potential therapeutic strategy for various skeletal muscle disorders.

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Spotlight on skeletal muscle disorders: from ribonuclear inclusion in myotonic dystrophy to treatment of McArdle?s Disease by oral sucrose

Journal of Neurology ◽

10.1007/s00415-004-0392-5 ◽

2004 ◽

Vol 251 (2) ◽

pp. 242-244

Author(s):

Michael Strupp

Keyword(s):

Skeletal Muscle ◽

Myotonic Dystrophy ◽

Muscle Disorders ◽

Oral Sucrose ◽

Skeletal Muscle Disorders

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Roles of Skeletal Muscle-Derived Exosomes in Organ Metabolic and Immunological Communication

Frontiers in Endocrinology ◽

10.3389/fendo.2021.697204 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wataru Aoi ◽

Yuko Tanimura

Keyword(s):

Skeletal Muscle ◽

Physical Fitness ◽

Skeletal Muscles ◽

Metabolic Dysfunction ◽

Nutrient Metabolism ◽

Muscle Disorders ◽

Bodily Fluids ◽

Muscular Function ◽

Circulating Levels ◽

Expression And Activity

Skeletal muscles secrete various factors, such as proteins/peptides, nucleotides, and metabolites, which are referred to as myokines. Many of these factors are transported into extracellular bodily fluids in a free or protein-bound form. Furthermore, several secretory factors have been shown to be wrapped up by small vesicles, particularly exosomes, secreted into circulation, and subsequently regulate recipient cells. Thus, exosome contents can be recognized as myokines. In recipient cells, proteins, microRNAs, and metabolites in exosomes can regulate the expression and activity of target proteins associated with nutrient metabolism and immune function. The levels of circulating exosomes and their contents are altered in muscle disorders and metabolic-related states, such as metabolic dysfunction, sarcopenia, and physical fitness. Therefore, such circulating factors could mediate various interactions between skeletal muscle and other organs and may be useful as biomarkers reflecting physiological and pathological states associated with muscular function. Here, this review summarizes secretory regulation of muscle-derived exosomes. Their metabolic and immunological roles and the significance of their circulating levels are also discussed.

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Activities of creatine kinase and its isoenzymes in serum in various skeletal muscle disorders.

Clinical Chemistry ◽

10.1093/clinchem/34.12.2460 ◽

1988 ◽

Vol 34 (12) ◽

pp. 2460-2462 ◽

Cited By ~ 20

Author(s):

J Arenas ◽

V Diaz ◽

G Liras ◽

E Gutierrez ◽

I Santos ◽

...

Keyword(s):

Skeletal Muscle ◽

Creatine Kinase ◽

Clinical Features ◽

Principal Factor ◽

Isoenzyme Pattern ◽

Type I ◽

Isoenzyme Analysis ◽

Muscle Disorders ◽

Total Creatine ◽

Skeletal Muscle Disorders

Abstract We studied possible correlations between anatomopathological and clinical features and the values for total creatine kinase (CK; EC 2.7.3.2) and its isoenzymes, including the proportion of CK-MB, in a population displaying several neuromuscular pathologies. Although we observed no specific isoenzyme pattern associated with the different myopathies, we found isoenzyme analysis useful in studying the histopathological evolution of illness. We also considered whether the pathology was regenerative or nonregenerative, and what type of fiber (I or II) was involved. High CK-MB percentages (greater than 6%) were associated with regenerative and type I fiber myopathies, with regenerative type tissues being the principal factor associated with an increasing proportion of CK-MB. Studying the changes in CK-MB percentage in serum appears to be useful in discriminating neuromuscular from myocardial pathologies.

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Is Gene-Size an Issue for the Diagnosis of Skeletal Muscle Disorders?

Journal of Neuromuscular Diseases ◽

10.3233/jnd-190459 ◽

2020 ◽

Vol 7 (3) ◽

pp. 203-216 ◽

Cited By ~ 2

Author(s):

Marco Savarese ◽

Salla Välipakka ◽

Mridul Johari ◽

Peter Hackman ◽

Bjarne Udd

Keyword(s):

Skeletal Muscle ◽

Muscle Disorders ◽

Gene Size ◽

Skeletal Muscle Disorders

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Gene Therapy of Skeletal Muscle Disorders Using Viral Vectors

Muscle ◽

10.1016/b978-0-12-381510-1.00076-4 ◽

2012 ◽

pp. 1045-1051 ◽

Cited By ~ 1

Author(s):

Andrea L.H. Arnett ◽

Julian N. Ramos ◽

Jeffrey S. Chamberlain

Keyword(s):

Skeletal Muscle ◽

Gene Therapy ◽

Viral Vectors ◽

Muscle Disorders ◽

Skeletal Muscle Disorders

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Effect of diltiazem on skeletal muscle 3-O-methylglucose transport in bacteremic rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.256.3.r716 ◽

1989 ◽

Vol 256 (3) ◽

pp. R716-R721

Author(s):

M. V. Westfall ◽

M. M. Sayeed

Keyword(s):

Escherichia Coli ◽

Skeletal Muscle ◽

Low Temperature ◽

Skeletal Muscles ◽

Cytochalasin B ◽

Sugar Transport ◽

Male Rats ◽

Saline Control ◽

Permeability Changes

This study examined whether alterations in cellular Ca2+ regulation contribute to previously observed changes in skeletal muscle sugar transport during bacteremia. Fasted male rats received saline (control) or bacteria (4 X 10(10) Escherichia coli/kg) intraperitoneally. Twelve hours later, basal and insulin-mediated 3-O-methylglucose (3MG) transport was measured in isolated soleus muscles. Measurements of 3MG transport in the presence of cytochalasin b or at a low temperature (0.5 degree C) indicated that altered sugar transport in bacteremic rat muscles was not due to nonspecific membrane permeability changes. To determine the role of Ca2+ in the pathogenesis of altered sugar transport during bacteremia, rats were treated with the Ca2+ antagonist diltiazem (DZ, 0.6-2.4 mg/kg) at various times (0, 0 + 7.5, 10 h) after saline or bacterial injection. In bacteremic rats given 2.4 mg/kg DZ at 10 h, basal and insulin-mediated transport were similar to control values. This dose of DZ had little effect on control muscles. The addition of 20 microM DZ to the incubation media did not affect basal or insulin-mediated 3MG transport in bacteremic rat muscles. Addition of the Ca2+ agonist BAY K 8644 to the incubation media had no effect on sugar transport in bacteremic rat muscles but caused alterations in control rat muscles that were comparable to those observed in bacteremia. These results suggest that alterations in Ca2+ regulation could contribute to the previously observed changes in sugar transport in skeletal muscles from bacteremic rats.

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Impact of Melatonin on Skeletal Muscle and Exercise

Cells ◽

10.3390/cells9020288 ◽

2020 ◽

Vol 9 (2) ◽

pp. 288 ◽

Cited By ~ 5

Author(s):

Alessandra Stacchiotti ◽

Gaia Favero ◽

Luigi Fabrizio Rodella

Keyword(s):

Quality Of Life ◽

Skeletal Muscle ◽

Human Aging ◽

Muscle Disorders ◽

Age Related ◽

Anti Oxidant ◽

Therapeutic Tools ◽

Skeletal Muscle Disorders ◽

Preclinical And Clinical Studies

Skeletal muscle disorders are dramatically increasing with human aging with enormous sanitary costs and impact on the quality of life. Preventive and therapeutic tools to limit onset and progression of muscle frailty include nutrition and physical training. Melatonin, the indole produced at nighttime in pineal and extra-pineal sites in mammalians, has recognized anti-aging, anti-inflammatory, and anti-oxidant properties. Mitochondria are the favorite target of melatonin, which maintains them efficiently, scavenging free radicals and reducing oxidative damage. Here, we discuss the most recent evidence of dietary melatonin efficacy in age-related skeletal muscle disorders in cellular, preclinical, and clinical studies. Furthermore, we analyze the emerging impact of melatonin on physical activity. Finally, we consider the newest evidence of the gut–muscle axis and the influence of exercise and probably melatonin on the microbiota. In our opinion, this review reinforces the relevance of melatonin as a safe nutraceutical that limits skeletal muscle frailty and prolongs physical performance.

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