Zhu Huabin, Lemos Henrique, Bhatt Brinda, Islam Bianca N, Singh Abhijit, Gurav Ashish, Huang Lei, Browning Darren D, Mellor Andrew, Fulzele Sadanand, Singh Nagendra
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, Georgia, United States of America.
Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
PLoS One. 2017 Sep 12;12(9):e0183484. doi: 10.1371/journal.pone.0183484. eCollection 2017.
Carbidopa is a drug that blocks conversion of levodopa to dopamine outside of central nervous system (CNS) and thus inhibits unwanted side effects of levodopa on organs located outside of CNS during management of Parkinson's Disease (PD). PD is associated with increased expression of inflammatory genes in peripheral and central nervous system (CNS), infiltration of immune cells into brain, and increased numbers of activated/memory T cells. Animal models of PD have shown a critical role of T cells in inducing pathology in CNS. However, the effect of carbidopa on T cell responses in vivo is unknown. In this report, we show that carbidopa strongly inhibited T cell activation in vitro and in vivo. Accordingly, carbidopa mitigated myelin oligodendrocyte glycoprotein peptide fragment 35-55 (MOG-35-55) induced experimental autoimmune encephalitis (EAE) and collagen induced arthritis in animal models. The data presented here suggest that in addition to blocking peripheral conversion of levodopa, carbidopa may inhibit T cell responses in PD individuals and implicate a potential therapeutic use of carbidopa in suppression of T cell mediated pathologies.
卡比多巴是一种药物，可阻断左旋多巴在中枢神经系统（CNS）外转化为多巴胺，从而在帕金森病（PD）的治疗过程中抑制左旋多巴对CNS外器官产生的不良副作用。PD与外周和中枢神经系统（CNS）中炎症基因表达增加、免疫细胞浸润入脑以及活化/记忆T细胞数量增多有关。PD动物模型已显示T细胞在诱导CNS病变中起关键作用。然而，卡比多巴对体内T细胞反应的影响尚不清楚。在本报告中，我们表明卡比多巴在体外和体内均强烈抑制T细胞活化。因此，在动物模型中，卡比多巴减轻了髓鞘少突胶质细胞糖蛋白肽片段35 - 55（MOG - 35 - 55）诱导的实验性自身免疫性脑脊髓炎（EAE）和胶原诱导的关节炎。此处呈现的数据表明，除了阻断左旋多巴的外周转化外，卡比多巴可能抑制PD患者的T细胞反应，并提示卡比多巴在抑制T细胞介导的病变方面具有潜在的治疗用途。
