Review
Lysophospholipids in the nervous system

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Abstract

This piece offers perspectives on the emerging roles of lysophospholipids, which include lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), for the biology and pathophysiology of the nervous system. It reflects opinions generated during a meeting sponsored by the National Institute on Drug Abuse (NIDA) entitled “Targeted Lipidomics: Signaling Lipids and Drugs of Abuse” held in Washington, D.C., 15–17 April 2004, organized by Dr. Rao Rapaka. Lysophospholipids represent one class of lipids that has many important actions mediated by G protein-coupled receptors. While influencing a large number of biologically important systems, this discussion will focus on the nervous system, including areas of future research.

Introduction

Lysophospholipids are small lipid molecules that have been shown, in recent years, to have a range of important effects on many different organ systems. The best studied examples of lysophospholipids are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), which are part of a host of related molecules that are defined by a 3-carbon backbone, glycerol or sphingoid in nature, to which an acyl chain having variable length and saturation is attached. A major focus in recent years has been the action of extracellular lysophospholipids through their cognate G protein coupled receptors (GPCRs): there are nine lysophospholipids receptors, 4 for LPA (LPA1–4) and 5 for S1P (S1P1–5), with a number of putative lysophospholipid GPCRs existing in the literature. Recent reviews have covered many facets of this rapidly growing field in detail [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17] and no attempt will be made to review this extensive literature. The purpose of this opinion piece is to stimulate discussion and increase awareness of areas relevant to Neuroscience, towards achieving an understanding of both the basic neurobiology of lysophospholipid signaling, and a framework for therapeutically useful strategies involving activated pathways.

Section snippets

Discussion

An essential distinction that must be made in assessing effects produced by lysophospholipids is whether their effects involve surface receptors – GPCRs – or non-GPCR mechanisms that could utilize different pathways, such as seen with S1P intracellular functions in Arabidopsis [18]. The necessity for this distinction, particularly in the nervous system where there exists enormous complexity of cellular interactions, is differentiating true signaling properties of lysophospholipids from

Acknowledgement

This work was supported by the NIMH.

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