LAUSR

In this issue of the BJD, Kim et al. used a positional scanning synthetic peptide combinatorial library to identify several small peptides that inhibited a-melanocyte stimulating hormone (a-MSH)-stimulated melanogenesis in normal and malignant melanocytes. According to the authors, this inhibition is mediated through the competition of melanocortin receptor type 1 (MC1-R) binding sites with a-MSH and other proopiomelanocortin (POMC)-derived products such as b-MSH, adrenocorticotropin and perhaps POMC precursor itself (Fig. 1). Such antagonistic activity is well appreciated for agouti signalling protein (ASP) and reported for c3MSH, a partial agonist on MC1-R, all inhibiting melanogenic activity of melanotropic peptides (Fig. 1). The advantages of using small antimelanogenic peptides for cosmetic application in hyperpigmentary disorders include the lack of toxicity, their small size, low cost, and a possibility to precisely control their activity through proper formulation and delivery to melanocytes residing on the basal layer of the epidermis or different compartments of the hair follicle. Such a targeted strategy is justified by the complex role of the POMC system in the skin with its precursor and products of processing being expressed in almost all resident cells and regulated in a precise fashion. However, one must consider the possible side-effects that are secondary to the expression of MC1-R on other cell types including keratinocytes, immune cells and fibroblasts. Melanocortins acting on this receptor exert anti-inflammatory and antifibrotic activities. Thus, competitive inhibition of MC1-R may induce pro-inflammatory and profibrotic phenotypes or aggravate existing inflammatory or fibrosing diseases (Fig. 1). Nevertheless, a new concept has been developed, proposing the inhibition of melanogenesis to improve effectiveness of immune-, chemoand radiotherapy in patients with melanoma. The concept appears to be justified by studies showing that melanin content in melanoma metastases affects the outcome of therapy. In this context, small antimelanogenic peptides can be tested for their efficacy in the treatment of metastatic melanotic melanomas as adjuvants. In conclusion, the search strategy and already identified small antimelanogenic peptides by Kim et al. open up new possibilities in dermatology.