Sphingolipids as Emerging Drug Targets: Therapeutic Applications of Ceramide Analogs

Sphingolipids, including ceramide, sphingomyelin, and glycosphingolipids, are essential components of eukaryotic cell membranes. At the cell surface, they form species- and cell type-specific patterns that change with cell growth, differentiation, transformation and oncogenesis. Apart from their structural role, they serve as attachment sites for many pathogens and are critically involved in the regulation of inter- and intracellular communication events like cell adhesion, proliferation, differentiation, and apoptosis. In recent years, their involvement in the formation of membrane microdomains, termed rafts, and their contribution to diverse signaling cascades attracted particular attention. Accumulating evidence further demonstrates an important role for sphingolipids in the modulation of pharmacologically relevant membrane-bound enzymes and receptors. We present a brief overview of new therapeutic strategies based on the intervention in sphingolipid metabolism. Emphasis is placed on ceramide analogs and on selected low molecular weight compounds interfering with ceramide metabolism.