IMR Press / FBE / Volume 15 / Issue 2 / DOI: 10.31083/j.fbe1502014
Open Access Review
NGR4 and ERBB4 as Promising Diagnostic and Therapeutic Targets for Metabolic Disorders
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1 Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia
2 Higher School of Living Systems, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia
*Correspondence: (Maria Vulf)
Front. Biosci. (Elite Ed) 2023, 15(2), 14;
Submitted: 30 August 2022 | Revised: 10 February 2023 | Accepted: 22 February 2023 | Published: 6 June 2023
(This article belongs to the Special Issue MicroRNAs and Other Non-coding RNAs in Human Health)
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Obese individuals are at high risk for developing type 2 diabetes mellitus, cardiovascular diseases, and nonalcoholic fatty liver disease. The aim of this review was to analyze the scientific literature and databases to reveal the fundamental role of neuregulin 4 (NRG4) and its receptors in the development of obesity-associated metabolic disorders. This review demonstrates that NRG4 and its receptors are promising therapeutic targets for the treatment of socially significant obesity-associated pathologies. The review contains nine chapters. Information on the structure of ERBB4 and NRG4 splice isoforms and subsequent activation of downstream targets is presented. The tissue-specific features of the NRG4 and ERBB4 genes and protein production are also highlighted. The role of NRG4 and ERBB3/4 in the pathophysiological mechanisms of the development of metabolic disorders in obesity is discussed in detail. The final chapter of the review is devoted to the miRNA-dependent regulation of NRG4 and ERBB4. Recent studies have shown that several miRNAs regulate ERBB4 expression, but no information was found on the interaction of NRG4 with miRNAs. We now demonstrate the putative relationships between NRG4 and let-7a-5p, let-7c-5p, miR-423-5p, miR-93-5p, miR-23a-3p, and miR-15b-5p for the first time. In addition, we found SNP mutations affecting the interaction of NRG4 and ERBB4 with miRNA in these genes as well as in miRNAs. In summary, this review provides a detailed and comprehensive overview of the role of NRG4 in obesity-associated metabolic disorders. The review summarizes all current studies on this topic and opens perspectives for future research.

ERBB signaling
type 2 DM
MK-2072.2022.3/Grant of the President of the Russian Federation
FZWM-2020-0010/State Assignment
Fig. 1.
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