Stratum Corneum Ceramides: Function, Origins, and Therapeutic Applications
2005
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.
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