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Altered Levels of Sphingosine, Sphinganine and Their Ceramides in Atopic Dermatitis Are Related to Skin Barrier Function, Disease Severity and Local Cytokine Milieu
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Loricrin: Past, Present, and Future

1
Department of Dermatology, Faculty of Medicine, University of Tsukuba 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
2
Department of Dermatology and Charles C. Gates Center for Regenerative Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(7), 2271; https://doi.org/10.3390/ijms21072271 (registering DOI)
Received: 6 February 2020 / Accepted: 19 March 2020 / Published: 25 March 2020
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
The terminal differentiation of the epidermis is a complex physiological process. During the past few decades, medical genetics has shown that defects in the stratum corneum (SC) permeability barrier cause a myriad of pathological conditions, ranging from common dry skin to lethal ichthyoses. Contrarily, molecular phylogenetics has revealed that amniotes have acquired a specialized form of cytoprotection cornification that provides mechanical resilience to the SC. This superior biochemical property, along with desiccation tolerance, is attributable to the proper formation of the macromolecular protein-lipid complex termed cornified cell envelopes (CE). Cornification largely depends on the peculiar biochemical and biophysical properties of loricrin, which is a major CE component. Despite its quantitative significance, loricrin knockout (LKO) mice have revealed it to be dispensable for the SC permeability barrier. Nevertheless, LKO mice have brought us valuable lessons. It is also becoming evident that absent loricrin affects skin homeostasis more profoundly in many more aspects than previously expected. Through an extensive review of aggregate evidence, we discuss herein the functional significance of the thiol-rich protein loricrin from a biochemical, genetic, pathological, metabolic, or immunological aspect with some theoretical and speculative perspectives. View Full-Text
Keywords: stratum corneum; cornified cell envelopes; loricrin; thiol; ε-(γ-glutamyl) lysine cross-linkage; disulfide cross-linkage; atopy; Langerhans cell stratum corneum; cornified cell envelopes; loricrin; thiol; ε-(γ-glutamyl) lysine cross-linkage; disulfide cross-linkage; atopy; Langerhans cell
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Ishitsuka, Y.; Roop, D.R. Loricrin: Past, Present, and Future. Int. J. Mol. Sci. 2020, 21, 2271.

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