ABSTRACT
Over the past 10þ years, the number of research reports related to ceramides (Cer) has dramatically increased in biological and biomedical fields. Most of these reports focus on the regulation of cellular proliferation, apoptosis, and cell senescence in a variety of cell types. The attention to Cer in the cutaneous research field began in the late 1970s. Pioneering analytical studies by Gray and co-workers (1-4) elucidated the Cer concept of epidermal lipids, which stimulated a host of other researchers. Later, Downing and Wertz, and others including ourselves (5-17), further explored the structural analysis of epidermal sphingolipids. A summary of these studies showed that the epidermis displays a unique Cer molecular profile, i.e., bulk amount, molecular heterogeneity, chemical structures, etc. Concurrently, the physiological relevance of epidermal sphingolipids for epidermal permeability barrier function was elucidated by Elias and co-workers (18-20), and those suffering from skin diseases with barrier defects, e.g., atopic dermatitis (21-24), psoriasis (25,26), and ichthyosis (27), were shown to have alterations in the stratum corneum (SC) Cer profile. These studies stimulated further epidermal sphingolipid research. The importance of sphingolipids in cellular function has led to the use of sphingolipids and their metabolic inhibitors for therapeutic purposes, e.g., in sphingolipidosis (28), cancer (29), and cardiovascular disease (30,31), with the development of approved drugs that have not yet been launched. Cer and its metabolic activators have already been utilized for improving epidermal permeability barrier function and/or to treat dry skin symptoms.Thepurpose of the following review is to summarize what is currently known about the unique Cer content of the SC, its origins, function, and therapeutic applications.
