Abstract
Melasma is a common skin disease involving changes in normal skin pigmentation. It results from epidermal melanocyte hyperactivity that causes increased production and accumulation of melanin. The onset of the disease has been associated with sun exposure, drugs, genetic and hormonal factors. The primary focus of this review was to provide an updated overview of the main biological aspects behind skin pigmentation and melasma development. As a second aim of this review, the main mechanisms by which different compounds could reduce melanogenesis were also discussed. Common hypo-pigmenting agents act by reducing the melanogenesis through several mechanisms; they can affect melanin transcription and glycosylation, inhibit tyrosinase (a pivotal enzyme in melanin synthesis), slow the melanosome transfer or increase the skin turnover. Although a number of skin-lightening agents were proposed for treatment of hyperpigmentary disorders, none of these has achieved satisfactory effects. In this light, the most recent therapeutic strategies for melasma, and emerging molecular targets to control skin pigmentation, such as MITF, Wnt and mTOR, were herein described.
Highlights
Melasma is a common skin disease involving changes in normal skin pigmentation
- a single layer of cells attached to a non-cellular basement membrane separating the epidermis from the dermis; - basal keratinocytes with stem cell-like properties, Merkel cells and melanocytes
Following the synthesis of melanins, filled melanosomes are introduced in the keratinocytes in the corresponding epidermal melanin unit, through the melanocyte dendritic extensions
Summary
The skin, in addition to provide a vast barrier against external physical threats, acts as a defence system against UV radiation (UV-R), through the high-molecular-weight brown pigment melanin [1,2]. The epidermis is the outermost layer, providing a waterproof barrier; it is a stratified epithelium devoid of blood or nerve supplies, and composed of several distinct cell populations, above all keratinocytes and melanocytes [4] It is arranged in four layers, as follows (Table 1): The dermis is beneath the epidermis and forms the neural, vascular, lymphatic, and secretory apparatus of the skin. It contains connective tissue, fibroblasts (required for synthesis and degradation of the extracellular matrix), macrophages and mast cells (able to trigger allergic reactions by secreting bioactive mediators), hair follicles (providing a protective niche to several stem cell populations required during wound healing), nails, excretory and secretory glands [1,3,5].
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