Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06355, Republic of Korea.
Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Exp Mol Med. 2023 Jun;55(6):1110-1130. doi: 10.1038/s12276-023-01018-9. Epub 2023 Jun 1.
Sphingolipids, which are components of cellular membranes and organ tissues, can be synthesized or degraded to modulate cellular responses according to environmental cues, and the balance among the different sphingolipids is important for directing immune responses, regardless of whether they originate, as intra- or extracellular immune events. Recent progress in multiomics-based analyses and methodological approaches has revealed that human health and diseases are closely related to the homeostasis of sphingolipid metabolism, and disease-specific alterations in sphingolipids and related enzymes can be prognostic markers of human disease progression. Accumulating human clinical data from genome-wide association studies and preclinical data from disease models provide support for the notion that sphingolipids are the missing pieces that supplement our understanding of immune responses and diseases in which the functions of the involved proteins and nucleotides have been established. In this review, we analyze sphingolipid-related enzymes and reported human diseases to understand the important roles of sphingolipid metabolism. We discuss the defects and alterations in sphingolipid metabolism in human disease, along with functional roles in immune cells. We also introduce several methodological approaches and provide summaries of research on sphingolipid modulators in this review that should be helpful in studying the roles of sphingolipids in preclinical studies for the investigation of experimental and molecular medicines.
鞘脂类是细胞膜和器官组织的组成部分，可根据环境信号合成或降解，以调节细胞反应，不同鞘脂类之间的平衡对于指导免疫反应很重要，而无论它们是作为细胞内还是细胞外免疫事件起源。基于多组学的分析和方法学方法的最新进展表明，人类健康和疾病与鞘脂代谢的动态平衡密切相关，鞘脂和相关酶的疾病特异性改变可以作为人类疾病进展的预后标志物。来自全基因组关联研究的累积人类临床数据和疾病模型的临床前数据为以下观点提供了支持，即鞘脂类是补充我们对免疫反应和已确定相关蛋白和核苷酸功能的疾病的理解的缺失部分。在这篇综述中，我们分析了与鞘脂相关的酶和报道的人类疾病，以了解鞘脂代谢的重要作用。我们讨论了人类疾病中鞘脂代谢的缺陷和改变，以及免疫细胞中的功能作用。我们还介绍了几种方法学方法，并在这篇综述中总结了鞘脂调节剂的研究，这对于研究鞘脂在实验和分子医学研究中的作用应该是有帮助的。
