Jang Hannah, Kim Sehwan, Lee Jae Man, Oh Yong-Seok, Park Sang Myun, Kim Sang Ryong
aSchool of Life Sciences bBK21 Plus KNU Creative BioResearch Group cInstitute of Life Science and Biotechnology dDepartment of Biochemistry and Cell Biology, School of Medicine, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program eBrain Science and Engineering Institute, Kyungpook National University fDepartment of Brain-Cognitive Science, Daegu-Gyeongbuk Institute of Science and Technology, Daegu gDepartment of Pharmacology hChronic Inflammatory Disease Research Center iBK21 Plus Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea.
Neuroreport. 2017 Mar 22;28(5):242-249. doi: 10.1097/WNR.0000000000000740.
Although the main cause of degeneration of the nigrostriatal dopaminergic (DA) projection in Parkinson's disease (PD) is still controversial, many reports suggest that excessive inflammatory responses mediated by activated microglia can induce neurotoxicity in the nigrostriatal DA system in vivo. Montelukast, which plays an anti-inflammatory role, is used to treat patients with asthma. In addition, recent studies have reported that its administration could reduce neuroinflammatory activities, showing beneficial effects against various neuropathological conditions. These results suggest that montelukast may be a useful drug to alleviate inflammatory responses in PD, even though there are no reports showing its beneficial effects against neurotoxicity in the nigrostriatal DA system. In the present study, our results showed that treatment with montelukast could protect DA neurons against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity and its administration significantly attenuated the production of neurotoxic cytokines such as tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) from activated microglia in the substantia nigra (SN) and striatum following 6-OHDA treatment. Therefore, we suggest that montelukast can be used as a potential inhibitor of microglial activation to protect DA neurons in the adult brain against PD.
尽管帕金森病（PD）中黑质纹状体多巴胺能（DA）投射变性的主要原因仍存在争议，但许多报告表明，活化的小胶质细胞介导的过度炎症反应可在体内黑质纹状体DA系统中诱导神经毒性。孟鲁司特具有抗炎作用，用于治疗哮喘患者。此外，最近的研究报告称，其给药可降低神经炎症活动，对各种神经病理状况显示出有益效果。这些结果表明，孟鲁司特可能是一种缓解PD炎症反应的有用药物，尽管尚无报告显示其对黑质纹状体DA系统神经毒性有有益作用。在本研究中，我们的结果表明，孟鲁司特治疗可保护DA神经元免受6-羟基多巴胺（6-OHDA）诱导的神经毒性，并且其给药显著减弱了6-OHDA处理后黑质（SN）和纹状体中活化小胶质细胞产生的神经毒性细胞因子，如肿瘤坏死因子-α（TNFα）和白细胞介素-1β（IL-1β）。因此，我们认为孟鲁司特可作为一种潜在的小胶质细胞活化抑制剂，以保护成年大脑中的DA神经元免受PD侵害。
