Oilseeds and fats, crops and lipids (Jan 2019)
Ceramides metabolism and impaired epidermal barrier in cutaneous diseases and skin aging: focus on the role of the enzyme PNPLA1 in the synthesis of ω-O-acylceramides and its pathophysiological involvement in some forms of congenital ichthyoses☆
Abstract
The outermost layer of the skin, the stratum corneum, is essential for the protective barrier functions of the skin. It results from the stacking of corneocytes, the dead flattened cells resulting from epidermal terminal differentiation of underlying living keratinocytes. The cornified lipid envelope, encapsulating corneocytes, and the extracellular mortar-like multilayered lipid matrix, called lamellae, are two crucial elements of the epidermal barrier. Stratum corneum extracellular lipids are mainly composed of ceramides, cholesterol and free fatty acids. Ceramides, and more specifically the epidermis specific ω-O-acylceramides, are essential for lipid-matrix organization into lamellae and formation of the corneocyte lipid envelope. Pathophysiological studies of inherited lipid metabolism disorders recently contributed to a better understanding of stratum corneum lipid metabolism. In the lab, our data from patients with Autosomal Recessive Congenital Ichthyosis and a murine knock-out model showed that the enzyme PNPLA1 is essential for the last step of synthesis of omega-O-acylceramides. Skin aging is a complex biological process caused by genetic and extrinsic factors e.g. sun exposure, smoke, and pollution. Aging skin is marked by a senescence-related decline in lipid and water content, which ultimately impairs epidermal barrier function. Thus, aged epidermis is prone to develop altered drug permeability, increased susceptibility to irritants contact dermatitis and severe xerosis. Ceramide deficiency may account, at least in part, for the dysfunction of the stratum corneum associated with ageing. Hence, treatments able to increase skin-ceramide levels could improve the epidermal barrier function in aged skin. Many animal testing and clinical trials are taken in that regard.
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