sphingosine-1-phosphate and Central-Nervous-System-Diseases

Sphingolipids are a class of lipids highly enriched in the central nervous system (CNS), which shows great diversity and complexity, and has been implicated in CNS development and function. Alterations in sphingolipid metabolism have been described in multiple diseases, including those affecting the central nervous system (CNS). In this review, we discuss the role of sphingolipid metabolism in neurodegeneration, evaluating its direct roles in neuron development and health, and also in the induction of neurotoxic activities in CNS-resident astrocytes and microglia in the context of neurologic diseases such as multiple sclerosis and Alzheimer's disease. Finally, we focus on the metabolism of gangliosides and sphingosine-1-phosphate, its contribution to the pathogenesis of neurologic diseases, and its potential as a candidate target for the therapeutic modulation of neurodegeneration.

Topics: Animals; Central Nervous System Diseases; Gangliosides; Humans; Lipid Metabolism; Lysophospholipids; Neurodegenerative Diseases; Sphingolipids; Sphingosine

The family of sphingosine-1-phosphate receptors (S1PRs) are G protein-coupled and comprise of five subtypes, S1P

Topics: Animals; Central Nervous System Agents; Central Nervous System Diseases; Clinical Trials as Topic; Humans; Lysophospholipids; Receptors, Lysosphingolipid; Sphingosine

The development of fingolimod, an unselective functional antagonist of the interactions between sphingosine 1 phosphate (S1P) and sphingosine 1 phosphate receptors (S1PRs), as the first oral therapy for multiple sclerosis (MS) has been a milestone. The parallel intensive research on the role of S1P, sphingosine kinases, and the five known S1PRs, their tissue distribution and expression in physiological and pathological conditions have led to a wide range of interesting findings. The initial focus of this research in the context of developing fingolimod as a treatment of MS has been on its immunological effects. The wide distribution and important roles of sphingosine, its metabolites, and their receptors in the central nervous system (CNS) in general, in myelin, and in all cell types of this organ have spurred interest to examine S1P and its five receptors in the brain as well. The present review will concentrate on the latter area and give a brief overview of what is known about S1P/S1PR interactions in the CNS in physiological and pathological conditions.

Topics: Animals; Central Nervous System Diseases; Humans; Lysophospholipids; Receptors, Lysosphingolipid; Sphingosine