Integrated sphingosine-1 phosphate signaling in the central nervous system: From physiological equilibrium to pathological damage

Sphingosine-1 phosphate (S1P), a bioactive sphingolipid metabolite, plays an essential role in cellular homeostasis. It is well evidenced that enzymes responsible for SIP production, as well as S1P receptors are expressed in the central nervous system (CNS), implying that SIP may contribute to CNS physiology. In current review, we will present the current knowledge about developmental and neuromodulatory functions of S1P in the brain. Considering neuroprotective effects of S1P, we also review the relation between S1P and cellular autophagy, mitochondrial function, oxidative stress and apoptosis as well as molecular pathways underlying neuroprotective effects of S1P. Given these pivotal functions, in the last section, we will summarize latest findings about possible contribution of SIP dysregulation in neurological disorders like Alzheimer's disease and multiple sclerosis. (C) 2015 Elsevier Ltd. All rights reserved.