Journal Article

Sphingosine 1-phosphate

Cartier, Andreane, Hla, Timothy

2019

Overview

Sphingosine 1-phosphate (S1P) is an important circulating lipid mediator that is derived from the metabolism of cell membranes. Its diverse homeostatic roles, particularly in immunology and vascular biology, can go awry in numerous diseases, including multiple sclerosis, cardiovascular diseases, and fibrosis. The centrality of S1P signaling has led to the development of several drugs, including two approved for treatment of multiple sclerosis. In a Review, Cartier and Hla discuss the current understanding of how one mediator can carry out so many signaling roles in different tissues, how these become dysregulated in disease, and efforts in drug development to target S1P signaling. Science , this issue p. eaar5551 Sphingosine 1-phosphate (S1P), a metabolic product of cell membrane sphingolipids, is bound to extracellular chaperones, is enriched in circulatory fluids, and binds to G protein–coupled S1P receptors (S1PRs) to regulate embryonic development, postnatal organ function, and disease. S1PRs regulate essential processes such as adaptive immune cell trafficking, vascular development, and homeostasis. Moreover, S1PR signaling is a driver of multiple diseases. The past decade has witnessed an exponential growth in this field, in part because of multidisciplinary research focused on this lipid mediator and the application of S1PR-targeted drugs in clinical medicine. This has revealed fundamental principles of lysophospholipid mediator signaling that not only clarify the complex and wide ranging actions of S1P but also guide the development of therapeutics and translational directions in immunological, cardiovascular, neurological, inflammatory, and fibrotic diseases.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Adaptive systems / Aging / Anatomy / Animals / Antagonists / Apolipoproteins / Apolipoproteins M - metabolism / Atrophy / Autoimmune diseases / Autoimmune Diseases - drug therapy / Autoimmune Diseases - physiopathology / Autoimmunity / Cardiovascular diseases / Cardiovascular Diseases - drug therapy / Cardiovascular Diseases - physiopathology / Cardiovascular Physiological Phenomena / Cardiovascular system / Cardiovascular System - embryology / Cardiovascular System - growth & development / Cardiovascular System - metabolism / Cell activation / Cell fate / Cell membranes / Central nervous system / Central Nervous System - growth & development / Central Nervous System - physiology / Chaperones / Clinical medicine / Compartments / Concentration gradient / Coronary artery disease / Disease / Drug Development / Drugs / Egress / Embryogenesis / Embryonic growth stage / Fibrosis / Fibrosis - drug therapy / Fibrosis - physiopathology / Heart / Heart diseases / Homeostasis / Humans / Immune system / Immune System Phenomena / Immunology / Inflammatory diseases / Isoforms / Lipids / Lung diseases / Lysophospholipids - metabolism / Metabolism / Mice / Modulators / Molecular Chaperones / Multidisciplinary research / Multiple sclerosis / Myocardium / Narcotics / Neurodegenerative diseases / Neurodegenerative Diseases - drug therapy / Neurodegenerative Diseases - physiopathology / Neurodevelopment / Neurodevelopmental disorders / Neuronal-glial interactions / Organs / Physiology / Proteins / Questions / R&D / Research & development / REVIEW SUMMARY / Signal Transduction / Sphingosine - analogs & derivatives / Sphingosine - metabolism / Sphingosine-1-Phosphate Receptors - antagonists & inhibitors / Sphingosine-1-Phosphate Receptors - metabolism / Therapy / Vertebrates