{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:29:03Z","timestamp":1786969743789,"version":"build-2736575974"},"reference-count":108,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>This review highlights the main aspects of the involvement of sphingosine-1-phosphate (S1P) metabolism in the reparative processes of the adult brain, including neurogenesis, oligodendrogenesis and angiogenesis, which are necessary for the normal functioning of the central nervous system. Neurogenesis is a complex, multifactorial, and multi-stage process of formation of neurons and neuroglial cells from neural stem cells. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and fibroblast growth factor (FGF), play a special role in the regulation of neurogenesis. The fine regulation of neurogenesis, which occurs at all its stages, includes the molecular mechanisms of cellular signaling mediated by S1P and its receptors. In particular, S1P and its receptors affect adult neurogenesis at multiple stages: activation of S1P receptors induces neuroblast proliferation, migration, and morphological changes. Special attention is paid to the interaction of S1P and its receptors with the cellular environment (astrocytes, endothelial cells, and ependyma) of the neurogenic niche and the relationship between S1P metabolism and the expression of neurotrophins, which suggests a key role of S1P in regulating the environment of the neurogenic niche.<\/jats:p>","DOI":"10.3390\/ijms27167342","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"7342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Potential Role of Sphingosine-1-Phosphate and Its Receptors in the Reparative Processes of the Adult Brain"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5641-7452","authenticated-orcid":false,"given":"Uliana A.","family":"Gutner","sequence":"first","affiliation":[{"name":"Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Shupik","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Alessenko","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.4103\/NRR.NRR-D-24-01438","article-title":"Brain structural plasticity in large-brained mammals: Not only narrowing roads","volume":"21","author":"Ghibaudi","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.stem.2026.01.014","article-title":"Adult neurogenesis: New neurons, new opportunities","volume":"33","author":"Doludda","year":"2026","journal-title":"Cell Stem Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/978-3-030-74046-7_8","article-title":"Intervention of Brain-Derived Neurotrophic Factor and Other Neurotrophins in Adult Neurogenesis","volume":"Volume 1331","author":"Aloe","year":"2021","journal-title":"Recent Advances in NGF and Related Molecules"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s12264-024-01206-1","article-title":"Quiescent Adult Neural Stem Cells: Developmental Origin and Regulatory Mechanisms","volume":"40","author":"Meng","year":"2024","journal-title":"Neurosci. Bull."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Fang, S., Wu, Z., Guo, Y., Zhu, W., Wan, C., Yuan, N., Chen, J., Hao, W., Mo, X., and Guo, X. (2023). Roles of microglia in adult hippocampal neurogenesis in depression and their therapeutics. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1193053"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"El Ouaamari, Y., Van den Bos, J., Willekens, B., Cools, N., and Wens, I. (2023). Neurotrophic Factors as Regenerative Therapy for Neurodegenerative Diseases: Current Status, Challenges and Future Perspectives. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043866"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sancho-Alonso, M., Arenas, Y.M., Izquierdo-Altarejos, P., Martinez-Garcia, M., Llansola, M., and Felipo, V. (2023). Enhanced Activation of the S1PR2-IL-1\u03b2-Src-BDNF-TrkB Pathway Mediates Neuroinflammation in the Hippocampus and Cognitive Impairment in Hyperammonemic Rats. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417251"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"G\u00fcner, F., and Rothhammer, V. (2025). Neurotrophic factors in multiple sclerosis. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1654603"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1007\/s12015-025-11022-3","article-title":"From Pluripotency to Precision: A Comprehensive Review of hPSCs\/iPSCs Models in Neuroscience Research","volume":"22","author":"Y","year":"2026","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/s41583-023-00744-3","article-title":"Neuron\u2013oligodendroglial interactions in health and malignant disease","volume":"24","author":"Taylor","year":"2023","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-neuro-112723-025806","article-title":"The Many Lives of an Oligodendrocyte Precursor Cell","volume":"48","author":"Buchanan","year":"2025","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Duncan, G.J., Simkins, T.J., and Emery, B. (2021). Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.653101"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"106050","DOI":"10.1016\/j.neuint.2025.106050","article-title":"Dynamic interaction of oligodendrocyte precursor cells with other cell types in the central nervous system","volume":"190","author":"Li","year":"2025","journal-title":"Neurochem. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.yjmcc.2021.10.009","article-title":"Endothelial repair by stem and progenitor cells","volume":"163","author":"Wang","year":"2022","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e70262","DOI":"10.1111\/jnc.70262","article-title":"Fundamental Neurochemistry Review: Sphingolipids and Ceramides in Brain Development","volume":"169","author":"Chinnappa","year":"2025","journal-title":"J. Neurochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"108381","DOI":"10.1016\/j.pharmthera.2023.108381","article-title":"The role of sphingosine 1-phosphate metabolism in brain health and disease","volume":"244","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1134\/S1068162021050277","article-title":"The Role of Sphingosine-1-Phosphate in Neurodegenerative Diseases","volume":"47","author":"Gutner","year":"2021","journal-title":"Russ. J. Bioorganic Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e16228","DOI":"10.1111\/jnc.16228","article-title":"Deciphering the role of sphingosine 1-phosphate in central nervous system myelination and repair","volume":"169","author":"Binish","year":"2025","journal-title":"J. Neurochem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gulliksen, E., Darsi, S., Haidarbaigi, L., Codispoti, L.J., Purohit, D., Jung, A., Chilamula, A., and Newton, J. (2026). Function and Modulation of Sphingosine-1-Phosphate Receptors in the Central Nervous System. Receptors, 5.","DOI":"10.3390\/receptors5010009"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"104775","DOI":"10.1016\/j.jbc.2023.104775","article-title":"Sphingosine-1-phosphate and its receptors in vascular endothelial and lymphatic barrier function","volume":"299","author":"Weigel","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s40263-021-00798-w","article-title":"Sphingosine 1-Phosphate Receptor Modulators for Multiple Sclerosis","volume":"35","author":"Roy","year":"2021","journal-title":"CNS Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/s41419-024-07310-4","article-title":"Sphk1\/S1P pathway promotes blood-brain barrier breakdown after intracerebral hemorrhage through inducing Nlrp3-mediated endothelial cell pyroptosis","volume":"15","author":"Feng","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Raza, Y., Salman, H., and Luberto, C. (2021). Sphingolipids in Hematopoiesis: Exploring Their Role in Lineage Commitment. Cells, 10.","DOI":"10.3390\/cells10102507"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4252\/wjsc.v10.i9.119","article-title":"Regulatory role of sphingosine kinase and sphingosine-1-phosphate receptor signaling in progenitor\/stem cells","volume":"10","author":"Ng","year":"2018","journal-title":"World J. Stem Cells"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sassoli, C., Pierucci, F., Zecchi-Orlandini, S., and Meacci, E. (2019). Sphingosine 1-Phosphate (S1P)\/ S1P Receptor Signaling and Mechanotransduction: Implications for Intrinsic Tissue Repair\/Regeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225545"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1002\/cbin.10991","article-title":"Sphingosine-1-phosphate promotes the proliferation and attenuates apoptosis of Endothelial progenitor cells via S1PR1\/S1PR3\/PI3K\/Akt pathway","volume":"42","author":"Wang","year":"2018","journal-title":"Cell Biol. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0014-5793(02)03404-X","article-title":"Embryonic brain expression analysis of lysophospholipid receptor genes suggests roles for s1p1 in neurogenesis and s1p1\u20133 in angiogenesis","volume":"531","author":"McGiffert","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e22616","DOI":"10.1096\/fj.202200533RR","article-title":"Sphingosine-1-phosphate receptor modulation improves neurogenesis and functional recovery after stroke","volume":"36","author":"Huang","year":"2022","journal-title":"FASEB J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/7651_2017_3","article-title":"Sphingosine-1-Phosphate (S1P) Signaling in Neural Progenitors","volume":"Volume 1697","author":"Turksen","year":"2017","journal-title":"Sphingosine-1-Phosphate"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1759091414558416","DOI":"10.1177\/1759091414558416","article-title":"Convergent Regulation of Neuronal Differentiation and Erk and Akt Kinases in Human Neural Progenitor Cells by Lysophosphatidic Acid, Sphingosine 1-Phosphate, and LIF: Specific Roles for the LPA1 Receptor","volume":"6","author":"Callihan","year":"2014","journal-title":"ASN Neuro"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5728","DOI":"10.1038\/s41467-025-60750-0","article-title":"HDL-bound S1P affects the subventricular niche and early neuropathological features of Alzheimer\u2019s disease","volume":"16","author":"Choi","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1002\/glia.23803","article-title":"Sphingosine 1-phosphate promotes the proliferation of olfactory ensheathing cells through YAP signaling and participates in the formation of olfactory nerve layer","volume":"68","author":"Bao","year":"2020","journal-title":"Glia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"110119","DOI":"10.1016\/j.cellsig.2021.110119","article-title":"Role of ceramide\/sphingomyelin (SM) balance regulated through \u201cSM cycle\u201d in cancer","volume":"87","author":"Taniguchi","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Karmeli\u0107, I., Jurilj Sajko, M., Sajko, T., Rotim, K., and Fabris, D. (2024). The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1466141"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.1176709","article-title":"Regulation of Histone Acetylation in the Nucleus by Sphingosine-1-Phosphate","volume":"325","author":"Hait","year":"2009","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.bbrc.2007.05.131","article-title":"HDL-like lipoproteins in cerebrospinal fluid affect neural cell activity through lipoprotein-associated sphingosine 1-phosphate","volume":"359","author":"Sato","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"eaar5551","DOI":"10.1126\/science.aar5551","article-title":"Sphingosine 1-phosphate: Lipid signaling in pathology and therapy","volume":"366","author":"Cartier","year":"2019","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1002\/1873-3468.14457","article-title":"The sphingolipid anteome: Implications for evolution of the sphingolipid metabolic pathway","volume":"596","author":"Santos","year":"2022","journal-title":"FEBS Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"eaav1263","DOI":"10.1126\/sciimmunol.aav1263","article-title":"CD4 T cell sphingosine 1-phosphate receptor (S1PR)1 and S1PR4 and endothelial S1PR2 regulate afferent lymphatic migration","volume":"4","author":"Xiong","year":"2019","journal-title":"Sci. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1134\/S0006297926600122","article-title":"Sphingosine-1-Phosphate Is a Key Signaling Molecule in Normal Conditions and in Multiple Sclerosis","volume":"91","author":"Ganin","year":"2026","journal-title":"Biochem. Mosc."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Pyne, N., and Pyne, S. (2017). Sphingosine 1-Phosphate Receptor 1 Signaling in Mammalian Cells. Molecules, 22.","DOI":"10.3390\/molecules22030344"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/s41589-021-00930-3","article-title":"Structural basis of sphingosine-1-phosphate receptor 1 activation and biased agonism","volume":"18","author":"Xu","year":"2022","journal-title":"Nat. Chem. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"eabf5325","DOI":"10.1126\/sciadv.abf5325","article-title":"Endogenous agonist\u2013bound S1PR3 structure reveals determinants of G protein\u2013subtype bias","volume":"7","author":"Maeda","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kleuser, B., and B\u00e4umer, W. (2023). Sphingosine 1-Phosphate as Essential Signaling Molecule in Inflammatory Skin Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021456"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1523\/JNEUROSCI.4645-04.2005","article-title":"Edg8\/S1P5: An Oligodendroglial Receptor with Dual Function on Process Retraction and Cell Survival","volume":"25","author":"Jaillard","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1172\/JCI10905","article-title":"Edg-1, the G protein\u2013coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation","volume":"106","author":"Liu","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kempf, A., Tews, B., Arzt, M.E., Weinmann, O., Obermair, F.J., Pernet, V., Zagrebelsky, M., Delekate, A., Iobbi, C., and Zemmar, A. (2014). The Sphingolipid Receptor S1PR2 Is a Receptor for Nogo-A Repressing Synaptic Plasticity. PLoS Biol., 12, Correction in PLoS Biol. 2014, 12, e1001818. https:\/\/doi.org\/10.1371\/journal.pbio.1001818.","DOI":"10.1371\/journal.pbio.1001818"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1523\/JNEUROSCI.0188-21.2021","article-title":"Endothelial Sphingosine-1-Phosphate Receptor 4 Regulates Blood-Brain Barrier Permeability and Promotes a Homeostatic Endothelial Phenotype","volume":"42","author":"Hansen","year":"2022","journal-title":"J. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1007\/s10571-022-01245-0","article-title":"Visualizing Sphingosine-1-Phosphate Receptor 1(S1P1) Signaling During Central Nervous System De- and Remyelination","volume":"43","author":"Hashemi","year":"2023","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Hurst, J.H., Mumaw, J., Machacek, D.W., Sturkie, C., Callihan, P., Stice, S.L., and Hooks, S.B. (2008). Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology. BMC Neurosci., 9.","DOI":"10.1186\/1471-2202-9-118"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e02179","DOI":"10.1002\/brb3.2179","article-title":"The emerging role of FTY720 as a sphingosine 1-phosphate analog for the treatment of ischemic stroke: The cellular and molecular mechanisms","volume":"11","author":"Naseh","year":"2021","journal-title":"Brain Behav."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1016\/j.ajpath.2015.06.009","article-title":"Sphingosine-1-Phosphate Receptor Antagonism Enhances Proliferation and Migration of Engrafted Neural Progenitor Cells in a Model of Viral-Induced Demyelination","volume":"185","author":"Blanc","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s00702-023-02618-5","article-title":"Repurposing drugs against Alzheimer\u2019s disease: Can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD?","volume":"130","author":"Kartalou","year":"2023","journal-title":"J. Neural Transm."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Pournajaf, S., Dargahi, L., Javan, M., and Pourgholami, M.H. (2022). Molecular Pharmacology and Novel Potential Therapeutic Applications of Fingolimod. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.807639"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/bph.15954","article-title":"Fingolimod ameliorates schizophrenia-like cognitive impairments induced by phencyclidine in male rats","volume":"180","author":"Yu","year":"2023","journal-title":"Br. J. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e70941","DOI":"10.1096\/fj.202501098RR","article-title":"BAF312 Inhibits the Growth of Glioma and Promotes the Normalization of Tumor Blood Vessels","volume":"39","author":"Qin","year":"2025","journal-title":"FASEB J."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Sindi, M., Hecker, C., Issberner, A., Ruck, T., Meuth, S.G., Albrecht, P., and Dietrich, M. (2023). S1PR-1\/5 modulator RP-101074 shows beneficial effects in a model of central nervous system degeneration. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1234984"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Lee, H.J., Choe, K., Park, J.S., Khan, A., Kim, M.W., Park, T.J., and Kim, M.O. (2022). O-Cyclic Phytosphingosine-1-Phosphate Protects against Motor Dysfunctions and Glial Cell Mediated Neuroinflammation in the Parkinson\u2019s Disease Mouse Models. Antioxidants, 11.","DOI":"10.3390\/antiox11112107"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11113","DOI":"10.1128\/MCB.25.24.11113-11121.2005","article-title":"Essential Role for Sphingosine Kinases in Neural and Vascular Development","volume":"25","author":"Mizugishi","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1159\/000231891","article-title":"Regulation of Stem Cell Pluripotency and Neural Differentiation by Lysophospholipids","volume":"17","author":"Pitson","year":"2009","journal-title":"Neurosignals"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3665","DOI":"10.1182\/blood-2003-02-0460","article-title":"G-protein-coupled receptor S1P1 acts within endothelial cells to regulate vascular maturation","volume":"102","author":"Allende","year":"2003","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s12519-022-00615-4","article-title":"Sphingosine phosphate lyase insufficiency syndrome: A systematic review","volume":"19","author":"Pournasiri","year":"2023","journal-title":"World J. Pediatr."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Atreya, K.B., and Saba, J.D. (2022). Neurological Consequences of Sphingosine Phosphate Lyase Insufficiency. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.938693"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1046\/j.1471-4159.2003.02219.x","article-title":"Sphingosine-1-phosphate induces proliferation and morphological changes of neural progenitor cells","volume":"88","author":"Harada","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6181","DOI":"10.1523\/JNEUROSCI.4491-12.2013","article-title":"An Activated Protein C Analog Stimulates Neuronal Production by Human Neural Progenitor Cells via a PAR1-PAR3-S1PR1 -Akt Pathway","volume":"33","author":"Guo","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5880","DOI":"10.1111\/ejn.14969","article-title":"The effects of microglia- and astrocyte-derived factors on neurogenesis in health and disease","volume":"54","author":"Araki","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.neuron.2014.02.039","article-title":"Prospective Identification and Purification of Quiescent Adult Neural Stem Cells from Their In Vivo Niche","volume":"82","author":"Codega","year":"2014","journal-title":"Neuron"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Huang, X., Guo, H., Cheng, X., Zhang, J., Qu, W., Ding, Q., Sun, Q., Shu, Q., and Li, X. (2022). NAD+ Modulates the Proliferation and Differentiation of Adult Neural Stem\/Progenitor Cells via Akt Signaling Pathway. Cells, 11.","DOI":"10.3390\/cells11081283"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1038\/sj.jcbfm.9600112","article-title":"Activation of the PI3-K\/Akt Pathway Mediates cGMP Enhanced-Neurogenesis in the Adult Progenitor Cells Derived from the Subventricular Zone","volume":"25","author":"Wang","year":"2005","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1634\/stemcells.2006-0223","article-title":"Essential Roles of Sphingosine 1-Phosphate\/S1P1 Receptor Axis in the Migration of Neural Stem Cells Toward a Site of Spinal Cord Injury","volume":"25","author":"Kimura","year":"2007","journal-title":"Stem Cells"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.cca.2021.03.025","article-title":"Sphingosine-1-phosphate receptor 3 signaling","volume":"519","author":"Li","year":"2021","journal-title":"Clin. Chim. Acta"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"13659","DOI":"10.1523\/JNEUROSCI.1353-15.2015","article-title":"Downregulation of Sphingosine 1-Phosphate Receptor 1 Promotes the Switch from Tangential to Radial Migration in the OB","volume":"35","author":"Alfonso","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"8440764","DOI":"10.1155\/sci\/8440764","article-title":"The Neurogenic Niche: Interactions Among Vessels, Glia, and Neural Stem Cells","volume":"2026","author":"Jahanbin","year":"2026","journal-title":"Stem Cells Int."},{"key":"ref_74","first-page":"468","article-title":"Roles of Ependymal Cells in the Physiology and Pathology of the Central Nervous System","volume":"14","author":"Deng","year":"2023","journal-title":"Aging Dis."},{"key":"ref_75","first-page":"100124","article-title":"Astrocytes: A potential avenue for depression and cancer","volume":"10","author":"Lu","year":"2025","journal-title":"Brain Behav. Immun. Integr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/jnc.14917","article-title":"Sphingosine 1-phosphate but not Fingolimod protects neurons against excitotoxic cell death by inducing neurotrophic gene expression in astrocytes","volume":"153","author":"Tran","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ijdevneu.2003.09.003","article-title":"Microglial activation state and lysophospholipid acid receptor expression","volume":"21","author":"Tham","year":"2003","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1093\/intimm\/dxz037","article-title":"Sphingosine 1-phosphate and inflammation","volume":"31","author":"Obinata","year":"2019","journal-title":"Int. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1186\/s12974-023-02964-x","article-title":"Neuroinflammation, memory, and depression: New approaches to hippocampal neurogenesis","volume":"20","author":"Wu","year":"2023","journal-title":"J. Neuroinflammation"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12987-025-00687-0","article-title":"Neisseria meningitidis regulates P-glycoprotein transporter activity in brain endothelial cells via sphingosine 1\u2013phosphate receptor 1","volume":"22","author":"Nosratabadi","year":"2025","journal-title":"Fluids Barriers CNS"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/aps.2012.186","article-title":"Sphingosine-1-phosphate induces VEGF-C expression through a MMP-2\/FGF-1\/FGFR-1-dependent pathway in endothelial cells in vitro","volume":"34","author":"Chang","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"102574","DOI":"10.1016\/j.stemcr.2025.102574","article-title":"Ependymal and neural stem cells are close relatives","volume":"20","author":"Lokka","year":"2025","journal-title":"Stem Cell Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/glia.23124","article-title":"Inflammatory demyelination induces ependymal modifications concomitant to activation of adult (SVZ) stem cell proliferation","volume":"65","author":"Pourabdolhossein","year":"2017","journal-title":"Glia"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-030-74046-7_1","article-title":"Nerve Growth Factor: The First Molecule of the Neurotrophin Family","volume":"Volume 1331","author":"Aloe","year":"2021","journal-title":"Recent Advances in NGF and Related Molecules"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s12974-015-0393-6","article-title":"Fingolimod induces neuroprotective factors in human astrocytes","volume":"12","author":"Hoffmann","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/glia.10180","article-title":"Sphingosine 1-phosphate induces the production of glial cell line-derived neurotrophic factor and cellular proliferation in astrocytes","volume":"41","author":"Yamagata","year":"2003","journal-title":"Glia"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Doi, Y., Takeuchi, H., Horiuchi, H., Hanyu, T., Kawanokuchi, J., Jin, S., Parajuli, B., Sonobe, Y., Mizuno, T., and Suzumura, A. (2013). Fingolimod Phosphate Attenuates Oligomeric Amyloid \u03b2\u2013Induced Neurotoxicity via Increased Brain-Derived Neurotrophic Factor Expression in Neurons. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061988"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1002\/jcb.23275","article-title":"Sphingosine kinase 1\/S1P pathway involvement in the GDNF-induced GAP43 transcription","volume":"112","author":"Murakami","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"14230","DOI":"10.1073\/pnas.1206093109","article-title":"Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome","volume":"109","author":"Deogracias","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1515\/biol-2022-0491","article-title":"S1P promotes corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model","volume":"17","author":"Lin","year":"2022","journal-title":"Open Life Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/s41419-020-02897-w","article-title":"Inhibition of HDAC increases BDNF expression and promotes neuronal rewiring and functional recovery after brain injury","volume":"11","author":"Sada","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/onc.2012.77","article-title":"The role of TRKA signaling in IL-10 production by apoptotic tumor cell-activated macrophages","volume":"32","author":"Ley","year":"2013","journal-title":"Oncogene"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1471-4159.2007.04496.x","article-title":"A cell-biological model of p75NTR signaling","volume":"102","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_94","first-page":"603","article-title":"Nerve growth factor, sphingomyelins, and sensitization in sensory neurons","volume":"60","author":"Nicol","year":"2008","journal-title":"Sheng Li Xue Bao"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"7996","DOI":"10.1074\/jbc.M111423200","article-title":"Sphingosine Kinase Interacts with TRAF2 and Dissects Tumor Necrosis Factor-\u03b1 Signaling","volume":"277","author":"Xia","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1113\/jphysiol.2006.111575","article-title":"Intracellular sphingosine 1-phosphate mediates the increased excitability produced by nerve growth factor in rat sensory neurons","volume":"575","author":"Zhang","year":"2006","journal-title":"J. Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1083\/jcb.200402016","article-title":"Differential transactivation of sphingosine-1-phosphate receptors modulates NGF-induced neurite extension","volume":"166","author":"Toman","year":"2004","journal-title":"J. Cell Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"15548","DOI":"10.1073\/pnas.2536483100","article-title":"TGF-\u03b2-induced RhoA and p160ROCK activation is involved in the inhibition of Cdc25A with resultant cell-cycle arrest","volume":"100","author":"Bhowmick","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.neuroscience.2009.12.020","article-title":"Sphingosine kinase 1 regulates the expression of proinflammatory cytokines and nitric oxide in activated microglia","volume":"166","author":"Nayak","year":"2010","journal-title":"Neuroscience"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Roggeri, A., Schepers, M., Tiane, A., Rombaut, B., van Veggel, L., Hellings, N., Prickaerts, J., Pittaluga, A., and Vanmierlo, T. (2020). Sphingosine-1-Phosphate Receptor Modulators and Oligodendroglial Cells: Beyond Immunomodulation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207537"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/glia.22949","article-title":"S1P1 deletion in oligodendroglial lineage cells: Effect on differentiation and myelination","volume":"64","author":"Dukala","year":"2016","journal-title":"Glia"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1002\/glia.20576","article-title":"Functional consequences of S1P receptor modulation in rat oligodendroglial lineage cells","volume":"55","author":"Jung","year":"2007","journal-title":"Glia"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.exer.2008.07.012","article-title":"Anti-sphingosine-1-phosphate monoclonal antibodies inhibit angiogenesis and sub-retinal fibrosis in a murine model of laser-induced choroidal neovascularization","volume":"88","author":"Caballero","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1161\/CIRCRESAHA.109.199778","article-title":"Bone Marrow Progenitor Cells Induce Endothelial Adherens Junction Integrity by Sphingosine-1-Phosphate\u2013Mediated Rac1 and Cdc42 Signaling","volume":"105","author":"Zhao","year":"2009","journal-title":"Circ. Res."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Williams, P.A., Stilhano, R.S., To, V.P., Tran, L., Wong, K., and Silva, E.A. (2015). Hypoxia Augments Outgrowth Endothelial Cell (OEC) Sprouting and Directed Migration in Response to Sphingosine-1-Phosphate (S1P). PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123437"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"118785","DOI":"10.1016\/j.biopha.2025.118785","article-title":"Fat for thought: Lipid regulation of neural stem cell fate","volume":"193","author":"Cabot","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5436","DOI":"10.1007\/s12035-018-1448-3","article-title":"The Role of Ceramide and Sphingosine-1-Phosphate in Alzheimer\u2019s Disease and Other Neurodegenerative Disorders","volume":"56","author":"Czubowicz","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"101636","DOI":"10.1016\/j.arr.2022.101636","article-title":"Neurogenesis in aging and age-related neurodegenerative diseases","volume":"78","author":"Culig","year":"2022","journal-title":"Ageing Res. Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7342\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:13:24Z","timestamp":1786968804000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7342"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":108,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167342"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167342","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]}}}