Fingolimod is an approved treatment for relapsing–remitting multiple sclerosis (MS), and its properties in different pathways have raised interest in therapy research for other neurodegenerative diseases. Fingolimod is an agonist of sphingosine-1-phosphate (S1P) receptors. Its main pharmacologic effect is immunomodulation by lymphocyte homing, thereby reducing the numbers of T and B cells in circulation. Because of the ubiquitous expression of S1P receptors, other effects have also been described. Here, we review preclinical experiments evaluating the effects of treatment with fingolimod in neurodegenerative diseases other than MS, such as Alzheimer’s disease or epilepsy. Fingolimod has shown neuroprotective effects in different animal models of neurodegenerative diseases, summarized here, correlating with increased brain-derived neurotrophic factor and improved disease phenotype (cognition and/or motor abilities). As expected, treatment also induced reductions in different neuroinflammatory markers because of not only inhibition of lymphocytes but also direct effects on astrocytes and microglia. Furthermore, fingolimod treatment exhibited additional effects for specific neurodegenerative disorders, such as reduction of amyloid-β production, and antiepileptogenic properties. The neuroprotective effects exerted by fingolimod in these preclinical studies are reviewed and support the translation of fingolimod into clinical trials as treatment in neurodegenerative diseases beyond neuroinflammatory conditions (MS).

芬戈莫德是一种经批准的治疗复发缓解型多发性硬化症 (MS) 的药物，其在不同途径中的特性引起了人们对其他神经退行性疾病治疗研究的兴趣。芬戈莫德是 1-磷酸鞘氨醇 (S1P) 受体的激动剂。其主要药理作用是通过淋巴细胞归巢进行免疫调节，从而减少循环中T细胞和B细胞的数量。由于 S1P 受体的普遍表达，其他效应也已被描述。在这里，我们回顾了评估芬戈莫德治疗多发性硬化症以外的神经退行性疾病（如阿尔茨海默病或癫痫）效果的临床前实验。芬戈莫德在不同的神经退行性疾病动物模型中显示出神经保护作用，此处总结，与脑源性神经营养因子的增加和疾病表型（认知和/或运动能力）的改善相关。正如预期的那样，治疗还导致不同神经炎症标志物的减少，因为不仅抑制淋巴细胞，而且还直接影响星形胶质细胞和小胶质细胞。此外，芬戈莫德治疗对特定的神经退行性疾病表现出额外的作用，例如减少淀粉样蛋白-β的产生和抗癫痫特性。对芬戈莫德在这些临床前研究中发挥的神经保护作用进行了回顾，并支持将芬戈莫德转化为临床试验，用于治疗神经炎症性疾病 (MS) 以外的神经退行性疾病。