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Autophagy as a Pathogenetic Link and a Target for Therapy of Musculoskeletal System Diseases

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Abstract

Autophagy is an evolutionarily conserved process of degradation of intracellular structures by lysosomal enzymes in specialized compartments such as autophagolysosomes plays a role in many processes, such as differentiation, maintenance of energy homeostasis, and protection of cells in the presence of destructive changes. Autophagy is of particular importance for the functioning of skeletal and cardiac muscles, namely, to maintain the structural and physiological integrity of the sarcomere during muscle contraction, as well as for pathological changes in the muscle fiber. Activation of the autophagy process occurs in response to a variety of stressful stimuli, such as muscle damage during intense exercise, resulting in tissue repair, including through the activation of satellite cells. In this review, autophagy is considered as a protective process, in which several types are distinguished, differing in their mechanisms. The review will cover the molecular basis of the autophagy process, its role in the vital activity and functioning of cells, as well as the therapeutic potential of autophagy activators in the treatment of severe human diseases associated with disorders of skeletal and cardiac muscles. Special attention will be paid to the description of pharmacological drugs that can enhance the activity of autophagy, as well as the mechanisms of their action.

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Abbreviations

AA:

amino acids

ROS:

reactive oxygen species

DMD:

Duchenne myodystrophy

AMPK:

AMP-activated protein kinase

Atg :

genes associated with autophagy

CASA:

chaperone-assisted selective autophagy

HSP:

heat shock proteins

mTOR:

mammalian target of rapamycin

ULK1:

Unc-51 like autophagy-initiating kinase 1

LC3:

microtubule-associated protein 1 light chain 3

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Funding

This work was supported by the Russian Science Foundation, grant No. 20-15-00271.

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Authors and Affiliations

  1. Almazov National Medical Research Center, St. Petersburg, Russia

    K. K. Kalugina, K. S. Sukhareva, A. I. Churkinа & A. A. Kostareva

  2. St. Petersburg State University, St. Petersburg, Russia

    K. K. Kalugina

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  1. K. K. Kalugina
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  2. K. S. Sukhareva
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  3. A. I. Churkinа
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  4. A. A. Kostareva
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Contributions

Writing a manuscript: K.K.K. and A.I.C.; surveying the relevant literature: K.K.K. and K.S.S.; editing a manuscript: A.A.K.

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Correspondence to K. K. Kalugina.

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CONFLICT OF INTEREST

The authors declare no evident or potential conflict of interest in relation with the publication of this review article.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2021, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2021, Vol. 107, Nos. 6–7, pp. 810–827https://doi.org/10.31857/S0869813921060042.

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Kalugina, K.K., Sukhareva, K.S., Churkinа, A.I. et al. Autophagy as a Pathogenetic Link and a Target for Therapy of Musculoskeletal System Diseases. J Evol Biochem Phys 57, 666–680 (2021). https://doi.org/10.1134/S0022093021030145

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