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Ceramides in Skin Health and Disease: An Update

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Abstract

Ceramides are a class of sphingolipid that is the backbone structure for all sphingolipids, such as glycosphingolipids and phosphosphingolipids. While being a minor constituent of cellular membranes, ceramides are the major lipid component (along with cholesterol, free fatty acid, and other minor components) of the intercellular spaces of stratum corneum that forms the epidermal permeability barrier. These stratum corneum ceramides consist of unique heterogenous molecular species that have only been identified in terrestrial mammals. Alterations of ceramide molecular profiles are characterized in skin diseases associated with compromised permeability barrier functions, such as atopic dermatitis, psoriasis and xerosis. In addition, hereditary abnormalities of some ichthyoses are associated with an epidermal unique ceramide species, omega-O-acylceramide. Ceramides also serve as lipid modulators to regulate cellular functions, including cell cycle arrest, differentiation, and apoptosis, and it has been demonstrated that changes in ceramide metabolism also cause certain diseases. In addition, ceramide metabolites, sphingoid bases, sphingoid base-1-phosphate and ceramide-1-phosphate are also lipid mediators that regulate cellular functions. In this review article, we describe diverse physiological and pathological roles of ceramides and their metabolites in epidermal permeability barrier function, epidermal cell proliferation and differentiation, immunity, and cutaneous diseases. Finally, we summarize the utilization of ceramides as therapy to treat cutaneous disease.

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Acknowledgements

We thank Ms Joan Wakefield for superb editorial assistance (Northern California Institute for Research and Education, San Francisco Veterans Affairs Health Care System, and the University of California San Francisco). We acknowledge the support of the Medical Research Services of the Veterans Affairs Medical Center, San Francisco.

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Authors and Affiliations

  1. Department of Dermatology, School of Medicine, University of California, San Francisco, USA

    Yoshikazu Uchida

  2. Northern California Institute for Research and Education, San Francisco, CA, USA

    Yoshikazu Uchida

  3. Dermatology Service (190), Veterans Affairs Medical Center, 1700 Owens Street, Room 326, San Francisco, CA, 94158, USA

    Yoshikazu Uchida

  4. Department of Food Science and Nutrition, Convergence Program of Material Science for Medicine and Pharmaceutics, Hallym University, Chuncheon, 24252, Korea

    Kyungho Park

  5. The Korean Institute of Nutrition, Hallym University, Chuncheon, Korea

    Kyungho Park

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  1. Yoshikazu Uchida
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Correspondence to Yoshikazu Uchida or Kyungho Park.

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This study was supported by the National Institutes of Health Grants R01 AR062025 (to YU), and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2018R1D1A1B7050504), the Ministry of Trade, Industry & Energy (MOTIE), Korea Institute for Advancement of Technology (KIAT) through the Encouragement Program (reference number P0014701) for The Industries of Economic Cooperation Region and Main Research Program (E0210600-01) of the Korea Food Research Institute (KFRI) funded by the Ministry of Science and ICT (to KP). This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Both YU and KP researched, wrote and re-wrote this manuscript.

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Uchida, Y., Park, K. Ceramides in Skin Health and Disease: An Update. Am J Clin Dermatol 22, 853–866 (2021). https://doi.org/10.1007/s40257-021-00619-2

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