Antimyostatin Treatment in Health and Disease: The Story of Great Expectations and Limited Success

Nielsen, T.; Vissing, John; Krag, Thomas

doi:10.3390/cells10030533

Cited by 29 publications

(21 citation statements)

References 187 publications

(112 reference statements)

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“…Myostatin is abundant in skeletal muscle, but it is also expressed in adipose tissue and heart muscle; it is widely conserved on the evolutionary scale, and the effect observed in mice is also found in dogs, sheep, cattle and humans [33]. However, attempts to apply the results obtained in animals to humans in order to test possible applications were rather disappointing [34].…”

Section: Myostatinmentioning

confidence: 99%

Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging

Mancinelli

Checcaglini

Coscia

et al. 2021

IJMS

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In the last decade, clear evidence has emerged that the cellular components of skeletal muscle are important sites for the release of proteins and peptides called “myokines”, suggesting that skeletal muscle plays the role of a secretory organ. After their secretion by muscles, these factors serve many biological functions, including the exertion of complex autocrine, paracrine and/or endocrine effects. In sum, myokines affect complex multi-organ processes, such as skeletal muscle trophism, metabolism, angiogenesis and immunological response to different physiological (physical activity, aging, etc.) or pathological states (cachexia, dysmetabolic conditions, chronic inflammation, etc.). The aim of this review is to describe in detail a number of myokines that are, to varying degrees, involved in skeletal muscle aging processes and belong to the group of proteins present in the functional environment surrounding the muscle cell known as the “Niche”. The particular myokines described are those that, acting both from within the cell and in an autocrine manner, have a defined relationship with the modulation of oxidative stress in muscle cells (mature or stem) involved in the regulatory (metabolic or regenerative) processes of muscle aging. Myostatin, IGF-1, NGF, S100 and irisin are examples of specific myokines that have peculiar features in their mechanisms of action. In particular, the potential role of one of the most recently characterized myokines—irisin, directly linked to an active lifestyle—in reducing if not reversing senescence-induced oxidative damage is discussed in terms of its possible application as an agent able to counteract the deleterious effects of muscle aging.

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Section: Myostatinmentioning

confidence: 99%

Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging

Mancinelli

Checcaglini

Coscia

et al. 2021

IJMS

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“…Although the detailed mechanisms of action of both rapamycin and SERMs are yet to be elucidated, they are of interest as disease-modifying drugs for DGpathy. Myostatin is a negative regulator of muscle growth, and myostatin inhibition therapy has been proposed for various diseases associated with muscle loss, such as muscular dystrophy [ 82 ]. With regards to DGpathy, a clinical trial of a myostatin inhibitor has been conducted in patients with FKRP mutation, but its effectiveness has not been observed to date [ 83 ].…”

Section: Treatment Methodsmentioning

confidence: 99%

Dystroglycanopathy: From Elucidation of Molecular and Pathological Mechanisms to Development of Treatment Methods

Kanagawa

2021

IJMS

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Dystroglycanopathy is a collective term referring to muscular dystrophies with abnormal glycosylation of dystroglycan. At least 18 causative genes of dystroglycanopathy have been identified, and its clinical symptoms are diverse, ranging from severe congenital to adult-onset limb-girdle types. Moreover, some cases are associated with symptoms involving the central nervous system. In the 2010s, the structure of sugar chains involved in the onset of dystroglycanopathy and the functions of its causative gene products began to be identified as if they were filling the missing pieces of a jigsaw puzzle. In parallel with these discoveries, various dystroglycanopathy model mice had been created, which led to the elucidation of its pathological mechanisms. Then, treatment strategies based on the molecular basis of glycosylation began to be proposed after the latter half of the 2010s. This review briefly explains the sugar chain structure of dystroglycan and the functions of the causative gene products of dystroglycanopathy, followed by introducing the pathological mechanisms involved as revealed from analyses of dystroglycanopathy model mice. Finally, potential therapeutic approaches based on the pathological mechanisms involved are discussed.

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“…Myostatin plays a central role in the regulation of muscle growth and therefore also in the regulation of metabolism. In the past years, there have also been several pharmacological developments concerning suppression of Myostatin as a target for curing muscular dystrophies [ 69 , 71 ].…”

Section: Myokinesmentioning

confidence: 99%

“…After 20 years of Myostatin research, a successful transition from mouse-model to human-model is still missing. Too many cofactors that need to be considered are still prohibiting the implementation of myostatin-inhibition in therapy [ 71 ]. This makes physical activity and exercise induced Myostatin-inhibition even more important for therapeutic use.…”

Section: Myokinesmentioning

confidence: 99%

Myokines and Resistance Training: A Narrative Review

Zunner

Wachsmuth

Eckstein

et al. 2022

IJMS

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In the last few years, the muscular system has gained attention due to the discovery of the muscle-secretome and its high potency for retaining or regaining health. These cytokines, described as myokines, released by the working muscle, are involved in anti-inflammatory, metabolic and immunological processes. These are able to influence human health in a positive way and are a target of research in metabolic diseases, cancer, neurological diseases, and other non-communicable diseases. Therefore, different types of exercise training were investigated in the last few years to find associations between exercise, myokines and their effects on human health. Particularly, resistance training turned out to be a powerful stimulus to enhance myokine release. As there are different types of resistance training, different myokines are stimulated, depending on the mode of training. This narrative review gives an overview about resistance training and how it can be utilized to stimulate myokine production in order to gain a certain health effect. Finally, the question of why resistance training is an important key regulator in human health will be discussed.

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Antimyostatin Treatment in Health and Disease: The Story of Great Expectations and Limited Success

Cited by 29 publications

References 187 publications

Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging

Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging

Dystroglycanopathy: From Elucidation of Molecular and Pathological Mechanisms to Development of Treatment Methods

Myokines and Resistance Training: A Narrative Review

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