Targeting ALDH1A1 to treat pigmentary disorders.

Clinical disorders related to skin pigmentation include hypo- or hyperpigmentation. Because they are difficult to treat, new approaches to develop safe pigment modulatory agents are needed. In the March issue of the journal, Paterson et al. (Exp Dermatol, 22, 2013) determined which aldehyde dehydrogenase 1A1 (ALDH1A1) substrates and products regulate melanogenesis. The authors demonstrated that ALDH1A1 substrate 9-cis retinal and its corresponding product 9-cis retinoic acid potently induced the accumulation of MITF mRNA, tyrosinase mRNA and melanin. Despite depletion of ALDH1A1, there was observed decreased ability of 9-cis retinal but not 9-cis retinoic acid to stimulate melanogenesis, indicating that ALDH1A1 regulates melanogenesis by catalysing the conversion of 9-cis retinal to 9-cis retinoic acid. Additionally, potent ALDH1A1 inhibitor such as cyanamide or Angeli's salt significantly suppressed pigmentation in human skin cells. These findings provide new candidate agents for the treatment of hypo- or hyperpigmentation disorders, using novel pigmentation-modulatory agents that target ALDH1A1.