Effects of LPA and SIP on the nervous system and implications for their involvement in disease

Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are two well-studied lysophospholipids that are known to be important regulators of cellular events. Their actions are mediated by activating a family of G-protein coupled receptors present in many cell types and tissues. These receptors have diverse biological roles owing to the heterogeneity of their signal transduction pathways. Many of these receptors are expressed in subsets of cells in the developing and mature mammalian nervous system and are thought to have important functions in its formation and maintenance. They are also widely expressed within other organ systems such as the immune system. Growing interest in the field has stimulated the development of a number of molecules that act as agonists or antagonists to LPA and S1P receptors. These molecules may lead to the development of new therapeutic compounds. Indeed, one such compound (FTY720) is currently in clinical trials for use in preventing transplant rejection and treating multiple sclerosis. The purpose of this manuscript is to: 1) review effects elicited by LPA and SIP on cells and tissues with a particular emphasis on the nervous System, 2) examine possible roles of these lipids in the development of disease, and 3) summarize the existing literature describing their agonists/antagonists.