Kappa opioid receptor activation alleviates experimental autoimmune encephalomyelitis and promotes oligodendrocyte-mediated remyelination.
Kappa opioid receptor activation alleviates experimental autoimmune encephalomyelitis and promotes oligodendrocyte-mediated remyelination.
复制标题
Kappa 阿片受体激活可缓解实验性自身免疫性脑脊髓炎并促进少突胶质细胞介导的髓鞘再生
DOI：
10.1038/ncomms11120
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发表时间：
2016-04-04
影响因子：
16.6
通讯作者：
Xie X
中科院分区：
文献类型：
--
作者：
Du C;Duan Y;Wei W;Cai Y;Chai H;Lv J;Du X;Zhu J;Xie X
多发性硬化症（MS）的特点是中枢神经系统的自身免疫性损伤。目前所有治疗多发性硬化症的药物都针对免疫系统。虽然可以有效减少新病变，但它们在预防残疾进展方面效果有限。促进少突胶质细胞介导的神经元髓鞘再生和恢复是多发性硬化症治疗的新方向。由MOR、DOR、KOR及其配体组成的内源性阿片系统被认为参与MS的发病机制。然而，确切的受体和机制仍然难以捉摸。在这里，我们发现 KOR 的基因缺失会加剧实验性自身免疫性脑脊髓炎，而用激动剂激活 KOR 可以缓解症状。 KOR 不影响免疫细胞的分化和功能。相反，它在体外和体内促进少突胶质细胞分化和髓鞘形成。我们的研究表明，针对 KOR 可能是开发新的多发性硬化症疗法的一种有趣方法，可以补充现有的免疫抑制方法。
Multiple sclerosis (MS) is characterized by autoimmune damage to the central nervous system. All the current drugs for MS target the immune system. Although effective in reducing new lesions, they have limited effects in preventing the progression of disability. Promoting oligodendrocyte-mediated remyelination and recovery of neurons are the new directions of MS therapy. The endogenous opioid system, consisting of MOR, DOR, KOR and their ligands, has been suggested to participate in the pathogenesis of MS. However, the exact receptor and mechanism remain elusive. Here we show that genetic deletion of KOR exacerbates experimental autoimmune encephalomyelitis, whereas activating KOR with agonists alleviates the symptoms. KOR does not affect immune cell differentiation and function. Instead, it promotes oligodendrocyte differentiation and myelination bothin vitroandin vivo. Our study suggests that targeting KOR might be an intriguing way to develop new MS therapies that may complement the existing immunosuppressive approaches.