ART4 and cheilitis: Acitretin was evaluated in a phase II clinical study and was found to increase ADAM10 expression as well as reduce the levels of Aβ in APP/PS-1 transgenic mice.223 Furthermore, it enhances the stimulation of the mature ADAM10, resulting in higher activity of α-secretase in neuroblastoma cells.223 One of the encouraging features of acitretin is its ability to cross the BBB easily, and its level is not affected by glycoprotein (P-gp).224 On the other side, it was linked to some severe toxicity, such as alopecia, peeling, cheilitis, and hepatotoxicity.154