A Theoretical Model for the Treatment of Androgenetic Alopecia Using the STEAP3 Protein, and the Genetic Challenges...

Androgenetic alopecia (AGA) is a prevalent condition. The treatment methods currently available for this condition have limited potential (minoxidil) and side effects with long-term therapy that affect the physiology of the male population (5α-reductase inhibitors). In recent years, there has been a considerable expansion in knowledge about the etiology of AGA, while current treatment methods appear to be outdated in light of new findings.

A review of the latest publications on androgenetic alopecia concerning its etiology and genetics was conducted, with the aim of examining the molecular pathways associated with mutations in the following genes: The following genes were found to be implicated: AR (WNT/β-catenin pathway), EDA2R (WNT/β-catenin and proapoptotic pathways), HDAC9 (Treg pathway), PAX1 and FOXA2 (development pathways). This facilitated the development of a theoretical model for the treatment of AGA using the STEAP3 protein.

A theoretical model of AGA therapy has been designed using the STEAP3 protein to activate the inhibited WNT/β-catenin pathway as a result of mutations in the AR and EDA2R genes. STEAP3 catalyses the conversion of Fe³⁺ to Fe²⁺, which in turn facilitates the phosphorylation of GSK3β, resulting in its subsequent inactivation. This process culminates in the dissolution of the complex that hinders the transfer of β-catenin to the cell nucleus.

It is hypothesised that STEAP3-based therapy has the potential to become an effective treatment for AGA, acting on the underlying cause of the disease (determined by the mutations described). It should be noted that all analyses presented in the following text constitute a theoretical model of AGA treatment using STEAP3 protein and its derivatives, and are not supported by laboratory and clinical studies. Nevertheless, they serve as an introduction to further in vitro, in vivo, and clinical trials.