Sphingosine-1-phosphate (S1P) and its receptor S1PR2 in central nervous system diseases: a review

Sphingosine-1-phosphate (S1P) is a key lipid signaling molecule that regulates a wide range of physiological and pathological processes through its interaction with G protein-coupled receptors, termed sphingosine-1-phosphate receptors (S1PRs). Among these receptors, S1PR2 is widely expressed in the central nervous system (CNS) and has been increasingly implicated in the pathogenesis of multiple CNS disorders. By regulating critical biological processes, including cell survival, proliferation, migration, inflammatory responses, and blood-brain barrier integrity, S1PR2 contributes to the development and progression of diseases such as stroke, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. This review summarizes the molecular structure of S1PR2 and the main features of its downstream signaling pathways, discusses its mechanistic roles and recent research advances in major CNS diseases, and highlights current therapeutic strategies and future directions for targeting S1PR2. This review aims to provide a theoretical basis for further mechanistic studies and the development of potential therapeutic interventions in CNS disorders.