The Pathogenic and Therapeutic Implications of Ceramide Abnormalities in Atopic Dermatitis

Abstract

Ceramides play an essential role in forming a permeability barrier in the skin. Atopic dermatitis (AD) is a common chronic skin disease associated with skin barrier dysfunction and immunological abnormalities. In patients with AD, the amount and composition of ceramides in the stratum corneum are altered. This suggests that ceramide abnormalities are involved in the pathogenesis of AD. The mechanism underlying lipid abnormalities in AD has not yet been fully elucidated, but the involvement of Th2 and Th1 cytokines is implicated. Ceramide-dominant emollients have beneficial effects on skin barrier function; thus, they have been approved as an adjunctive barrier repair agent for AD. This review summarizes the current understanding of the mechanisms of ceramide abnormalities in AD. Furthermore, the potential therapeutic approaches for correcting ceramide abnormalities in AD are discussed.

Novel Interactions of Myristic Acid and FADS3 Variants Predict Atopic Dermatitis among Indonesian Infants

“…The bent structure of the acyl chain due to the cis double bond is suggested to decrease the packing density of the lipid bilayer and weaken the lipid–lipid interaction [ 53 ]. While the relevance of this particular sphingoid base in AD still requires further study, altered sphingoid base profiles have been observed in relation to skin barrier abnormality in AD [ 55 , 56 ]. Our results point toward a possible role of FADS3 in AD etiology, with myristic acid representing a potential novel target for personalized preventive approaches.…”

Skin barrier defects in atopic dermatitis: From old idea to new opportunity

“…Much of the AD lipid research has focused on the ceramides abnormalities 49 and led to development of numerous ceramide-containing moisturizers, with the assumption they would improve dry skin and barrier function. 74 There is a real need for randomized double blind placebo control studies of these products to evaluate their effect on skin barrier function and AD clinical improvement.…”

Ceramide Acyl Chain Length and Its Relevance to Intracellular Lipid Regulation

“…Recently, there has been considerable interest in a subtype of sphingolipids known as ceramides, and in particular ceramide level derangements in skin and metabolic health. While the pleiotropic effects of ceramides have been reviewed extensively [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ], knowledge of its abundance in relation to intracellular lipid partitioning and regulation remains patchy. This review starts with a summary on the significance of ceramides in well-studied areas such as skin abnormalities and metabolic disease, before a focus on current knowledge surrounding intracellular lipid regulation and its relation to intracellular ceramide levels.…”