Drug targeting of sphingolipid metabolism: sphingomyelinases and ceramidases.

摘要: Sphingolipids represent a class of diverse bioactive lipid molecules that are increasingly appreciated as key modulators physiologic and pathophysiologic processes include cell growth, death, autophagy, angiogenesis, stress inflammatory responses. Sphingomyelinases ceramidases enzymes sphingolipid metabolism regulate the formation degradation ceramide, one most intensely studied classes sphingolipids. Improved understanding these control not only levels ceramide but also complex interconversion metabolites has provided foundation for functional analysis roles Our current various sphingolipids in regulation different cellular come from loss-of-function/gain-of-function studies utilizing genetic deletion/downregulation/overexpression (e.g. knockout animals, RNA interference) use pharmacologic inhibitors same enzymes. While approaches to evaluate have been instrumental advancing field, equally important identifying new processes.The latter promises development novel therapeutic targets with implications cancer therapy, inflammation, diabetes, neurodegeneration. In this review, we focus on status compounds inhibit sphingomyelinases ceramidases, will review history, uses future directions small molecule inhibitors, highlight which metabolizing used effectively treat models human disease.