Abstract

Androgenetic alopecia (AGA) remains an unsolved problem for the well-being of humankind, although multiple important involvements in hair growth have been discovered. Up until now, there is no ideal therapy in clinical practice in terms of efficacy and safety. Ultimately, there is a strong need for developing a feasible remedy for preventing and treating AGA. The Wnt/β-catenin signaling pathway is critical in hair restoration. Thus, AGA treatment via modulating this pathway is rational, although challenging. Dickkopf-related protein 1 (DKK1) is distinctly identified as an inhibitor of canonical Wnt/β-catenin signaling. Thus, in order to stimulate the Wnt/β-catenin signaling pathway, inhibition of DKK1 is greatly demanding. Studying DKK1-targeting microRNAs (miRNAs) involved in the Wnt/β-catenin signaling pathway may lay the groundwork for the promotion of hair growth. Bearing in mind that DKK1 inhibition in the balding scalp of AGA certainly makes sense, this review sheds light on the perspectives of miRNA-mediated hair growth for treating AGA via regulating DKK1 and, eventually, modulating Wnt/β-catenin signaling. Consequently, certain miRNAs regulating the Wnt/β-catenin signaling pathway via DKK1 inhibition might represent attractive candidates for further studies focusing on promoting hair growth and AGA therapy.

Highlights

  • Hair growth is a relatively complex process

  • The results showed that treatment with recombinant human secreted frizzled-related protein 2 (SFRP2) remarkably increased wingless and integrated-1 (Wnt)/β-catenin signaling [41]

  • Inhibition of Dickkopf-related protein 1 (DKK1) levels in the balding area of the scalp in populations that are at high risk of developing Androgenetic alopecia (AGA) might prevent the further progression of this disorder

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Summary

Introduction

Hair growth is a relatively complex process. The human hair cycle comprises three main phases: anagen, catagen, and telogen [1]. DKK1 is a natural inhibitor of Wnt, and strongly suppresses the Wnt/β-catenin signaling pathway via disrupting the Wnt-induced frizzled-low-density lipoprotein receptor-related proteins (LRP) 5/6 complex formation This adversely impacts HF morphogenesis and, influences the hair cycle [11]. Apart from the mentioned involvements in various physiological conditions, dysregulation of Wnt/β-catenin signaling is strongly associated with the development of AGA—a dermatological disorder whereby the hair is abnormally shed from the skin where it normally should be presented It is suppressed in AGA [13,22,24,25,26,27]. The recombinant DKK1 has inhibited the canonical Wnt/β-catenin signaling pathway that promotes hair growth in normal physiological condition. As a result of Wnt/β-catenin signaling suppression, the anagen phase is shortened and the apoptosis of follicular keratinocytes takes place [12]

Negative Influence of DKK1 on Hair Growth
Compounds Capable to Inhibit DKK1 Expression and Promote Hair Growth
Available and Recently Studied Therapeutics for AGA
Main Challenge
Concluding Remarks and Future Directions
Full Text
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