College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Yeonsu-gu, Incheon 21936, Korea.
Int J Mol Sci. 2021 Jul 23;22(15):7864. doi: 10.3390/ijms22157864.
Activation of microglia and/or astrocytes often releases proinflammatory molecules as critical pathogenic mediators that can promote neuroinflammation and secondary brain damages in diverse diseases of the central nervous system (CNS). Therefore, controlling the activation of glial cells and their neuroinflammatory responses has been considered as a potential therapeutic strategy for treating neuroinflammatory diseases. Recently, receptor-mediated lysophospholipid signaling, sphingosine 1-phosphate (S1P) receptor- and lysophosphatidic acid (LPA) receptor-mediated signaling in particular, has drawn scientific interest because of its critical roles in pathogenies of diverse neurological diseases such as neuropathic pain, systemic sclerosis, spinal cord injury, multiple sclerosis, cerebral ischemia, traumatic brain injury, hypoxia, hydrocephalus, and neuropsychiatric disorders. Activation of microglia and/or astrocytes is a common pathogenic event shared by most of these CNS disorders, indicating that lysophospholipid receptors could influence glial activation. In fact, many studies have reported that several S1P and LPA receptors can influence glial activation during the pathogenesis of cerebral ischemia and multiple sclerosis. This review aims to provide a comprehensive framework about the roles of S1P and LPA receptors in the activation of microglia and/or astrocytes and their neuroinflammatory responses in CNS diseases.
小胶质细胞和/或星形胶质细胞的激活通常会释放促炎分子，这些分子作为关键的致病介质，可以促进中枢神经系统（CNS）多种疾病中的神经炎症和继发性脑损伤。因此，控制神经胶质细胞的激活及其神经炎症反应被认为是治疗神经炎症性疾病的一种潜在治疗策略。最近，受体介导的溶血磷脂信号转导、特别是鞘氨醇 1-磷酸（S1P）受体和溶血磷脂酸（LPA）受体介导的信号转导，由于其在多种神经疾病（如神经病理性疼痛、全身性硬皮病、脊髓损伤、多发性硬化症、脑缺血、创伤性脑损伤、缺氧、脑积水和神经精神疾病）的发病机制中具有重要作用，引起了科学界的兴趣。小胶质细胞和/或星形胶质细胞的激活是大多数这些 CNS 疾病共有的一种常见发病事件，表明溶血磷脂受体可能影响神经胶质细胞的激活。事实上，许多研究报告称，几种 S1P 和 LPA 受体可以影响脑缺血和多发性硬化症发病过程中的神经胶质细胞激活。本综述旨在提供一个全面的框架，说明 S1P 和 LPA 受体在 CNS 疾病中小胶质细胞和/或星形胶质细胞的激活及其神经炎症反应中的作用。
