Partial Proteasome Inhibitors Induce Hair Follicle Growth by Stabilizing Beta-Catenin

The study demonstrated that the timing of hair growth cycles is influenced by the stability of signaling substrates regulated by the ubiquitin-proteasome system. Researchers found that applying partial proteasomal inhibitors (PaPIs) topically could inhibit proteasome activity in the skin, which in turn prevented the degradation of β-catenin, a crucial signal for the hair growth phase (anagen). This led to faster hair growth and a significantly shorter resting phase (telogen). The study revealed that PaPIs increase β-catenin levels, have a similar effect to the GSK3β antagonist LiCl, and counteract the inhibition of anagen by Dickopf-related protein. Consequently, PaPIs were identified as a new category of hair growth-promoting agents that work by temporarily altering the balance between stem cell activation and quiescence pathways.