Biology of melanogenesis and the search for hypopigmenting agents

Increased production and accumulation of melanin are characteristics of a large number of skin diseases, including melasma, post-inflammatory hyperpigmentation and lentigo. A number of clinical agents can reduce normal or abnormal pigmentation, but none of these have achieved satisfactory effects. This review discusses the mechanisms behind the different approaches. Tyrosinase is a pivotal enzyme in melanin synthesis. The majority of whitening or lightening agents act by specifically reducing the activity of tyrosinase via several mechanisms: (1) prior to melanin synthesis (interfering with its transcription and/or glycosylation); (2) during melanin synthesis (tyrosinase inhibition, peroxidase inhibition and reduction of byproducts); and (3) after melanin synthesis (tyrosinase degradation, inhibition of melanosome transfer, acceleration of skin turnover). Additional melanogenesis-associated mechanisms are also discussed.