Retinoids Modulate MITF: A Novel Mechanism in the Regulation of Melanogenesis

The study explored the regulation of melanogenesis, focusing on the role of Tyrosinase (TYR) and Aldehyde dehydrogenase 1A1 (ALDH1A1). It found that partial depletion of TYR in mice did not significantly reduce melanin accumulation, suggesting TYR might not be an ideal target for treating hyperpigmentary disorders. A genome-wide siRNA screen identified 92 novel regulators of melanogenesis, with ALDH1A1 being notable for its impact on TYR expression. Inhibiting ALDH1A1 with cyanamide reduced pigment and melanin synthesis in melanoma cells and human skin models, indicating its potential as a therapeutic target for hyperpigmentation disorders like melasma. The study also discovered that 9-cis retinoic acid, a product of ALDH1A1, stimulates melanin synthesis via the MITF-A promoter, regulated by RAR and RXR nuclear receptors. This suggests that retinoids or their analogs could be effective in treating both hyperpigmentary and hypopigmentary disorders, including vitiligo.