Abnormal Sphingolipid World in Inflammation Specific for Lysosomal Storage Diseases and Skin Disorders

Abstract

Research in recent years has shown that sphingolipids are essential signalling molecules for the proper biological and structural functioning of cells. Long-term studies on the metabolism of sphingolipids have provided evidence for their role in the pathogenesis of a number of diseases. As many inflammatory diseases, such as lysosomal storage disorders and some dermatologic diseases, including psoriasis, atopic dermatitis and ichthyoses, are associated with the altered composition and metabolism of sphingolipids, more studies precisely determining the responsibilities of these compounds for disease states are required to develop novel pharmacological treatment opportunities. It is worth emphasizing that knowledge from the study of inflammatory metabolic diseases and especially the possibility of their treatment may lead to insight into related metabolic pathways, including those involved in the formation of the epidermal barrier and providing new approaches towards workable therapies.

Keywords: inflammatory diseases; lysosomal storage diseases; skin disorders; sphingolipid metabolism alterations; treatments; workable therapies.

Figure 1

Overview of sphingolipid metabolism.

Figure 2

(A) Sphingolipid metabolic pathway in normal and psoriatic keratinocyte. In psoriatic keratinocytes, the level of ceramides is lowered, while the level of S1P is increased. (B) Possible effect of metabolic disturbances of sphingolipids on the development of psoriasis. Red arrow indicates a reduced level of ceramides, while green arrow presents an elevated level of S1P.