Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Behav Brain Res. 2013 Sep 1;252:415-21. doi: 10.1016/j.bbr.2013.06.016. Epub 2013 Jun 15.
Alzheimer's disease (AD) as a neurodegenerative brain disorder is the most common cause of dementia. To date, there is no causative treatment for AD and there are few preventive treatments either. The sphingosine-1-phosphate receptor modulator FTY720 (fingolimod) prevents lymphocytes from contributing to an autoimmune reaction and has been approved for multiple sclerosis treatment. In concert with other studies showing the anti-inflammatory and protective effect of FTY720 in some neurodegenerative disorders like ischemia, we have recently shown that FTY720 chronic administration prevents from impairment of spatial learning and memory in AD rats. Here FTY720 was examined on AD rats in comparison to the only clinically approved NMDA receptor antagonist, Memantine. Passive avoidance task showed significant memory restoration in AD animals received FTY720 comparable to Memantine. Upon gene profiling by QuantiGene Plex, this behavioral outcomes was concurrent with considerable alterations in some genes transcripts like that of mitogen activated protein kinases (MAPKs) and some inflammatory markers that may particularly account for the detected decline in hippocampal neural damage or memory impairment associated with AD. From a therapeutic standpoint, our findings conclude that FTY720 may suggest new opportunities for AD management probably based on several modulatory effects on genes involved in cell death or survival.
阿尔茨海默病（AD）是一种神经退行性脑疾病，是痴呆症最常见的病因。迄今为止，AD 没有病因治疗方法，也很少有预防治疗方法。鞘氨醇-1-磷酸受体调节剂 FTY720（芬戈莫德）可防止淋巴细胞参与自身免疫反应，已被批准用于多发性硬化症的治疗。与其他研究表明 FTY720 在某些神经退行性疾病（如缺血）中的抗炎和保护作用一致，我们最近表明，FTY720 慢性给药可预防 AD 大鼠的空间学习和记忆损伤。在这里，FTY720 与唯一临床上批准的 NMDA 受体拮抗剂美金刚在 AD 大鼠上进行了比较。被动回避任务显示，接受 FTY720 治疗的 AD 动物的记忆得到了显著恢复，与美金刚相当。通过 QuantiGene Plex 进行基因谱分析，这种行为结果与一些基因转录物的显著改变一致，例如丝裂原活化蛋白激酶（MAPKs）和一些炎症标志物，这些标志物可能特别解释了与 AD 相关的海马神经损伤或记忆障碍的检测下降。从治疗的角度来看，我们的发现表明 FTY720 可能为 AD 管理提供新的机会，这可能基于对参与细胞死亡或存活的基因的几种调节作用。
