RT Journal Article T1 Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm? A1 Martín Hernández, David A1 Muñoz López, Marina A1 Tendilla Beltrán, Hiram A1 Caso Fernández, Javier Rubén A1 García Bueno, Borja A1 Menchén Viso, Luis Alberto A1 Leza Cerro, Juan Carlos AB Over the past few decades, extensive research has shed light on immune alterations and the significance of dysfunctional biological barriers in psychiatric disorders. The leaky gut phenomenon, intimately linked to the integrity of both brain and intestinal barriers, may play a crucial role in the origin of peripheral and central inflammation in these pathologies. Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates both the immune response and the permeability of biological barriers. Notably, S1P-based drugs, such as fingolimod and ozanimod, have received approval for treating multiple sclerosis, an autoimmune disease of the central nervous system (CNS), and ulcerative colitis, an inflammatory condition of the colon, respectively. Although the precise mechanisms of action are still under investigation, the effectiveness of S1P-based drugs in treating these pathologies sparks a debate on extending their use in psychiatry. This comprehensive review aims to delve into the molecular mechanisms through which S1P modulates the immune system and brain/intestinal barrier functions. Furthermore, it will specifically focus on psychiatric diseases, with the primary objective of uncovering the potential of innovative therapies based on S1P signaling. PB MDPI SN 1422-0067 YR 2023 FD 2023-08-10 LK https://hdl.handle.net/20.500.14352/105466 UL https://hdl.handle.net/20.500.14352/105466 LA eng NO Martín-Hernández, D.; Muñoz-López, M.; Tendilla-Beltrán, H.; Caso, J.R.; García-Bueno, B.; Menchén, L.; Leza, J.C. Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm? Int. J. Mol. Sci. 2023, 24, 12634. https://doi.org/10.3390/ijms241612634 NO Ministerio de Ciencia e Innovación (España) NO Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) DS Docta Complutense RD 11 abr 2025