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The Role of Sphingosine-1-Phosphate in Neurodegenerative Diseases

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Abstract—

Sphingosine-1-phosphate (S1P) is a biologically active sphingolipid metabolite with antiapoptotic action. As a signal molecule, S1P regulates the survival of cells and their differentiation, the motility and dynamics of the cytoskeleton and is involved in the processes of cell migration, proliferation, and autophagy. The content of S1P in the cell is controlled by specific kinases and phosphatases as well as the enzyme of S1P degradation, S1P lyase. S1P fulfils most of its functions as a ligand to specific membrane G-protein-coupled receptors (S1PR1–5). S1P receptors are expressed by all cell types, including neurons and glial cells. In the central nervous system (CNS), S1P can perform protective functions and induce survival-stimulating signaling pathways or, conversely, contribute to the development of pathological processes, including neurodegenerative disorders. The functions of S1P, the expression of its receptors, and their action depend on the type of CNS cells, the stage of their development, and the state of the whole organism. Based on the action of S1P, the drug fingolimod was developed, which, by binding to S1P receptors with high affinity, diminishes the inflammatory cell infiltration, damage to tissues, and demyelination. The review highlights recent advances in the understanding of how S1P acts and its role in neurodegenerative disorders (Alzheimer’s disease, Parkinson’s disease, and lateral amyotrophic sclerosis).

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ACKNOWLEDGMENTS

The authors are grateful to Prof. A.V. Alesenko for advices they received when writing this paper.

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    U. A. Gutner & M. A. Shupik

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Translated by S. Sidorova

Abbreviations: AD, Alzheimer’s disease; ALS, amyotrophic lateral; sclerosis; PD, Parkinson’s disease; NDD, neurodegenerative diseases; S1P, sphingosine-1-phosphate; S1PR, sphingosine-1-phosphate receptor; SK, sphingosine kinase; SM, sphingomyelin; Аβ, β-amyloid peptide; АРР, amyloid precursor protein; PLC, phospholipase С; SOD, superoxide dismutase.

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Gutner, U.A., Shupik, M.A. The Role of Sphingosine-1-Phosphate in Neurodegenerative Diseases. Russ J Bioorg Chem 47, 1155–1171 (2021). https://doi.org/10.1134/S1068162021050277

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