Hair follicle stem cells (HFSCs) are undifferentiated, self-renew and multipotent cells in skin. Androgenetic Alopecia (AGA) is affecting 85% of males and 40% of females throughout the world. Its exact cause is unknown Androgens play a pivotal role in AGA etiology, but it is associated with other diseases, such as; hyper-androgenemia, hypothyroidism, prostate cancer, nutritional deficiencies, autoimmune diseases and even COVID-19. Multiple treatments have been considered for androgenetic alopecia, but, it was not satisfactory results. In individuals with AGA, hair follicle stem cells in bulge remain but are quiescent and it has been suggested that this may make AGA reversible. The activation of these cells through re-activation of signaling pathways such as wnt/β-catenin pathway may be the most effective treatment strategy for AGA. Five known signaling pathways which control HFSCs functions, are; wnt/β-catenin, sonic hedgehog (shh), notch, bone morphogenesis protein(BMP) and apoptosis signaling pathways. The Wnt pathway plays an important role in hair growth and regulates HFSC expression during the telogen-anagen phase transition, Shh pathway induces quiescent HFSCs to be activated and initiate to proliferate, Notch signaling plays a vital role in the activation, proliferation, differentiation of HFSCs and metabolite generation, then determines the fate of HFSCs and BMP is involved in HFSCs differentiation. The most recent attempt to treat AGA is to activate quiescent HFSCs in bulge using signaling pathways such as wnt/β-catenin. The golden goal of all research is to gain a deeper understanding of disease pathomechanisms to encourage the development of more effective treatments with greater specificity and less or zero adverse effects. This is ambitious but achievable dream.
