Wnt/β-Catenin Signaling Pathway Targeting Androgenetic Alopecia: How Far Can We Go Beyond Minoxidil and Finasteride?

The prevalence of AGA is continuously rising, with an earlier age of onset. Currently, only minoxidil and finasteride have received FDA approval for the treatment of AGA, inadequately addressing the pressing clinical needs. Recently, the involvement of the Wnt/β-catenin signaling pathway in AGA has attracted increased research interest. This perspective manuscript provides a comprehensive evaluation of the potential of targeting the Wnt/β-catenin pathway for next-generation AGA therapies. We systematically outlined its central role in regulating the hair follicle cycle and emphasized the therapeutic potential and mechanisms of key targets, including DKK, Dvl-CXXC5, Axin and GSK-3β. Moreover, we discussed the structural design and modification of various pathway activators, including DKK inhibitors and GSK-3β inhibitors, and presented extensive molecular docking analyses to elucidate the SARs. The insights presented will contribute to a comprehensive and unique perspective on the future discovery and development of therapeutics for AGA.