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首页> 外文期刊>The Canadian Journal of Neurological Sciences: le Journal Canadien des Sciences Neurologiques >Sphingosin-1-phosphate Receptor 1: a Potential Target to Inhibit Neuroinflammation and Restore the Sphingosin-1-phosphate Metabolism
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Sphingosin-1-phosphate Receptor 1: a Potential Target to Inhibit Neuroinflammation and Restore the Sphingosin-1-phosphate Metabolism

机译：Sphingosin-1-磷酸受体1：一个潜在的目标，以抑制神经炎症和恢复Sphingosin-1-磷酸的代谢。

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Background: Recent evidence suggests that an extreme shift may occur in sphingosine metabolism in neuroinflammatory contexts. Sphingosine 1-phosphate (S1P)-metabolizing enzymes (SMEs) regulate the level of S1P. We recently found that FTY720, a S1P analogue, and SEW2871, a selective S1P receptor 1 (S1P1) agonist, provide protection against neural damage and memory deficit in amyloid beta (A beta)-injected animals. This study aimed to evaluate the effects of these two analogues on the expression of SMEs as well as their anti-inflammatory roles. Methods: Rats were treated with intracerebral lipopolysaccharide (LPS) or A beta. Memory impairment was assessed by Morris water maze and the effects of drugs on SMEs as well as inflammatory markers, TNF-alpha and COX-II, were determined by immunoblotting. Results: A beta and LPS differentially altered the expression profile of SMEs. In A beta-injected animals, FTY720 and SEW2871 treatments exerted anti-inflammatory effects and restored the expression profile of SMEs, in parallel to our previous findings. In LPS animals however, in spite of anti-inflammatory effects of the two analogues, only FTY720 restored the levels of SMEs and prevented memory deficit. Conclusion: The observed ameliorating effects of FTY720 and SEW7821 can be partly attributed to the interruption of the vicious cycle of abnormal S1P metabolism and neuro-inflammation. The close imitation of the FTY720 effects by SW2871 in A beta-induced neuro-inflammation may highlight the attractive role of S1P1 as a potential target to restore S1P metabolism and inhibit inflammatory processes.
机译：背景：最新证据表明，在神经炎性环境中，鞘氨醇代谢可能发生极大变化。 1-磷酸鞘氨醇（S1P）代谢酶（SMEs）调节S1P的水平。我们最近发现，FTY720是一种S1P类似物，而SEW2871是一种选择性S1P受体1（S1P1）激动剂，可为注射了淀粉样蛋白β（A beta）的动物提供抗神经损伤和记忆缺陷的保护作用。这项研究旨在评估这两种类似物对中小企业的表达及其抗炎作用的影响。方法：用脑内脂多糖（LPS）或A beta治疗大鼠。通过莫里斯水迷宫评估记忆障碍，并通过免疫印迹测定药物对中小企业的影响以及炎性标志物TNF-α和COX-II。结果：β和LPS差异地改变了中小型企业的表达谱。与我们之前的发现相似，在注射了Aβ的动物中，FTY720和SEW2871处理发挥了抗炎作用，并恢复了SMEs的表达谱。然而，在LPS动物中，尽管这两种类似物具有抗炎作用，但只有FTY720恢复了SMEs的水平并防止了记忆缺陷。结论：FTY720和SEW7821观察到的改善作用部分归因于S1P代谢异常和神经炎症的恶性循环的中断。 SW2871在Aβ诱导的神经炎症中对FTY720效应的密切模仿可能突显了S1P1作为恢复S1P代谢和抑制炎症过程的潜在靶点的诱人作用。

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