Signaling Pathways in Melanogenesis

Abstract

Melanocytes are melanin-producing cells found in skin, hair follicles, eyes, inner ear, bones, heart and brain of humans. They arise from pluripotent neural crest cells and differentiate in response to a complex network of interacting regulatory pathways. Melanins are pigment molecules that are endogenously synthesized by melanocytes. The light absorption of melanin in skin and hair leads to photoreceptor shielding, thermoregulation, photoprotection, camouflage and display coloring. Melanins are also powerful cation chelators and may act as free radical sinks. Melanin formation is a product of complex biochemical events that starts from amino acid tyrosine and its metabolite, dopa. The types and amounts of melanin produced by melanocytes are determined genetically and are influenced by a variety of extrinsic and intrinsic factors such as hormonal changes, inflammation, age and exposure to UV light. These stimuli affect the different pathways in melanogenesis. In this review we will discuss the regulatory mechanisms involved in melanogenesis and explain how intrinsic and extrinsic factors regulate melanin production. We will also explain the regulatory roles of different proteins involved in melanogenesis.

Critical Analysis of the Melanogenic Pathway in Insects and Higher Animals

“…We are beginning to understand some aspects of hormonal regulation of melanogenesis in mammalian system [123,124,125]. Even melanogenic precursors, tyrosine and dopa seem to act as hormone-like regulators of melanogenic pathway in mammals [126].…”

Coptis chinensis inhibits melanogenesis increasing miR-340-mediated suppression of microphathalmia-associated transcription factor

“…During melanogenesis, melanin is produced from L-tyrosine by the key enzyme tyrosinase (Pillaiyar et al 2017;Kwon et al 2014;D'Mello et al 2016), and various skin-whitening raw materials have been developed to inhibit the expression and activity of tyrosinases (Gunia-Krzyżak et al 2016;Lee et al 2016;Choi et al 1998). The present study shows that C. chinensis extracts inhibit melanogenesis by decreasing tyrosinase activity (Fig.…”

“…Dopaquinone is then converted to dopachrome in the presence of thiol groups, and this metabolite is then converted by a tyrosinase-related protein (TRP)-2 into 5,6-dihydroxyindole-2-carboxylic acid, which is in turn converted by TRP-1 to indole-5,6-quinone-2-carboxylic acid to produce melanin (Tsukamoto et al 1992;Boissy et al 1998). The cyclic monophosphate/protein kinase A (cAMP/PKA) pathway is the main mode of signal transduction for melanin production, wherein cAMP, through PKA and cAMP-responsive element-binding protein 1 (CREB1), enhances the expression of microphthalmia-associated transcription factor (MITF) (D'Mello et al 2016). MITF is a critical transcription factor for melanogenesis and is known to enhance the transcription of tyrosinase and its related proteins TRP-1 and TRP-2 (Buscà and Ballotti 2000;Saha et al 2006).…”

Plumbagin Suppresses α-MSH-Induced Melanogenesis in B16F10 Mouse Melanoma Cells by Inhibiting Tyrosinase Activity

“…Abnormal melanogenesis, either increased or decreased production of melanin, is closely associated with a number of skin diseases including melanoma and the pigmentation disorders, such as chloasma and freckles [2,3]. Biosynthesis of melanin is initiated by multiple stimuli including UV irradiation, inflammatory cytokines, and hormonal signaling.…”