Targeting kallikrein proteases for dandruff therapy

Kallikrein proteases (KPs) are vital enzymes involved in the formation of dermatosomes and are regulated by the body's internal inhibitors. Maintaining a balance between KPs and their inhibitors is essential for promoting a healthy scalp. The scalp specifically contains two KPs: human kallikrein (hK) 5 and hK7, which are encoded by their respective genes. In addition, the serine protease inhibitor Kazal-type 5 (SPINK5) gene encodes the lympho-epithelial Kazal-type‒related inhibitor (LEKTI), which effectively inhibits both hK5 and hK7. The normal desquamation process relies on the availability and activity of hK5 and hK7, along with their regulation by LEKTI. When LEKTI levels are insufficient, it results in abnormal desquamation characterized by the overactivity of hK5 and hK7. Consequently, KPs, particularly hK5 and hK7, present promising targets for novel treatments aimed at reducing flake formation associated with dandruff. KP inhibitors are crucial components in targeting these proteases. In this review, literature on KPs, dandruff, and their inhibitors was analyzed to elucidate the roles of KPs in dandruff pathogenesis and to evaluate the therapeutic potential of KP inhibitor-based approaches for managing this condition.