Journal Article Corneocyte lipid envelope (CLE), the key structure for skin barrier function and ichthyosis pathogenesis

Akiyama, Masashi

88pp.3 - 9 , 2017-10 , Elsevier
Research on the genetic abnormalities and pathogenetic processes of ichthyoseshas progressed remarkably, and many causative genes and molecules have beenidentified in ichthyoses and ichthyosis syndromes. Most of the genes/moleculescausative of ichthyosis are associated with the barrier function of the stratumcorneum, and defects in the skin barrier play important roles in the pathogenesis ofvarious ichthyosis phenotypes.It has been elucidated that, of the ichthyosis-causative genes, ABCA12, ALOXE3,ALOX12B, CYP4F22, CERS3, ABHD5, PNPLA1 and ELOVL4 work in the formationof the corneocyte lipid envelope (CLE), a structure that is essential to sound skinbarrier function. The CLE mostly consists of ultra-long-chain (ULC) ceramidesderived from ULC-acylceramide (EOS; a combination of esterified ω-hydroxy fattyacids and sphingosines).In this review, I shed light on the synthesis, metabolism and transport ofepidermal ceramides, especially on ULC-acylceramide and the processes of CLEformation. In addition, I summarize the pathogeneses of various ichthyoses andichthyosis syndromes from the aspects of abnormal synthesis of ULC-acylceramideand malformation of the CLE.Investigations on the pathomechanisms of ichthyoses have provided novelknowledge on the synthesis and metabolism of ceramides in the epidermis.Conversely, research on the dynamics of epidermal ceramides has contributed to theelucidation of the pathogenesis of ichthyoses.Advances in our understanding of the biology of epidermal lipids and the diseasepathogeneses of ichthyoses and ichthyosis syndromes promise to provide clues forthe development of effective therapies for ichthyosis patients in the near future.

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