Current Status and Perspectives in Ceramide-Targeting Molecular Medicine

Hirofumi      Sawai; Naochika      Domae; Toshiro      Okazaki

Abstract

Ceramide is not only structurally but also functionally a key molecule in diverse kinds of sphingolipids. In the past decade, ceramide has been shown to be of crucial significance in several cell functions including apoptosis, cell growth, senescence, and cell cycle control. Among them, the role of ceramide in apoptosis induction has extensively been studied, and ceramide-targeting molecular medicine for apoptosis-based diseases such as malignant tumors, atherosclerosis and neurodegenerative disorders appears to come out to the clinical field. We here describe the recent advances in research of ceramide-mediated apoptosis signaling. We also show the relation of ceramide level through regulation of ceramide-related enzymes (sphingomyelinase, ceramidase, sphingomyelin synthase and glucosylceramide synthase) with diseases such as cancer, leukemia, bacterial infections, AIDS, Alzheimers disease, atherosclerosis, diabetes mellitus and atopic dermatitis. The strategies to construct the ceramide-targeting medicine for intractable diseases such as cancer and leukemia are discussed.

Keywords: ceramide, sphingomyelin, sphingomyelinase, ceramidase, sphingosine-1-phosphate, glucosylceramide, apoptosis, anticancer drug