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Review
. 2022 Jun 23:13:876078.
doi: 10.3389/fphys.2022.876078. eCollection 2022.

Myostatin and its Regulation: A Comprehensive Review of Myostatin Inhibiting Strategies

Mohammad Hassan Baig  1 , Khurshid Ahmad  2   3 , Jun Sung Moon  4 , So-Young Park  5 , Jeong Ho Lim  2   3 , Hee Jin Chun  2   3 , Afsha Fatima Qadri  2 , Ye Chan Hwang  2 , Arif Tasleem Jan  6 , Syed Sayeed Ahmad  2 , Shahid Ali  2 , Sibhghatulla Shaikh  2 , Eun Ju Lee  2   3 , Inho Choi  2   3
Affiliations
Review

Myostatin and its Regulation: A Comprehensive Review of Myostatin Inhibiting Strategies

Mohammad Hassan Baig et al. Front Physiol. .

Abstract

Myostatin (MSTN) is a well-reported negative regulator of muscle growth and a member of the transforming growth factor (TGF) family. MSTN has important functions in skeletal muscle (SM), and its crucial involvement in several disorders has made it an important therapeutic target. Several strategies based on the use of natural compounds to inhibitory peptides are being used to inhibit the activity of MSTN. This review delivers an overview of the current state of knowledge about SM and myogenesis with particular emphasis on the structural characteristics and regulatory functions of MSTN during myogenesis and its involvements in various muscle related disorders. In addition, we review the diverse approaches used to inhibit the activity of MSTN, especially in silico approaches to the screening of natural compounds and the design of novel short peptides derived from proteins that typically interact with MSTN.

Keywords: MSTN inhibitors; myostatin; natural compounds; peptides; skeletal muscle.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Smad and non-Smad mediated signaling pathway of MSTN. MSTN binds to the ACVRIIB and ALK4/5 complex resulting in successive phosphorylation of Smad2/3, leading to its binding with Smad4 and translocation of the complex to the nucleus. Non-Smad signaling, on the other hand, tends to suppress the AKT intracellular signaling pathways. Both Smad and non-Smad mediated signaling cause gene transcriptional alterations in the nucleus, as well as activation of muscle atrophy marker genes (MuRF1 and Atrogin1), resulting in muscle loss. Extracellularly, MSTN pathway inhibitors can bind MSTN directly or bind its receptor complex to prevent MSTN from interacting with its receptor complex and triggering downstream signals.
FIGURE 2
FIGURE 2
A typical approach for the conventional drug design and development strategy. An overview of the techniques for identifying MSTN inhibitors using in silico (virtual screening, molecular docking, ADMET, and so on), in vitro, and in vivo approaches.
FIGURE 3
FIGURE 3
A flowchart depicting the workflow for in silico peptide design.
See this image and copyright information in PMC

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