Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense de Madrid (UCM), Instituto de Investigación Hospital 12 de Octubre (i+12), Instituto Universitario de Investigación en Neuroquímica (IUIN), 28040 Madrid, Spain.
Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III (CIBERSAM, ISCIII), 28029 Madrid, Spain.
Int J Mol Sci. 2023 Aug 10;24(16):12634. doi: 10.3390/ijms241612634.
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.
在过去的几十年中，大量研究揭示了免疫改变以及生物功能障碍性屏障在精神疾病中的意义。肠漏现象与脑和肠道屏障的完整性密切相关，它可能在这些疾病中外周和中枢炎症的起源中发挥关键作用。鞘氨醇-1-磷酸（S1P）是一种调节免疫反应和生物屏障通透性的生物活性脂质。值得注意的是，基于 S1P 的药物，如芬戈莫德和奥扎尼莫德，分别已被批准用于治疗多发性硬化症（一种中枢神经系统自身免疫性疾病）和溃疡性结肠炎（一种结肠炎症性疾病）。尽管其确切的作用机制仍在研究中，但 S1P 类药物在治疗这些疾病方面的有效性引发了关于将其在精神病学中应用扩展的争论。本综述旨在深入探讨 S1P 调节免疫系统和脑/肠屏障功能的分子机制。此外，它将特别关注精神疾病，主要目的是揭示基于 S1P 信号的创新治疗方法的潜力。
