Kappa opioid receptor activation alleviates experimental autoimmune encephalomyelitis and promotes oligodendrocyte-mediated remyelination

Changsheng Du, Yanhui Duan, Wei Wei, Yingying Cai, Hui Chai, Jie Lv, Xiling Du, Jian Zhu and Xin Xie ()
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Changsheng Du: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University
Yanhui Duan: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University
Wei Wei: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University
Yingying Cai: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University
Hui Chai: CAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Jie Lv: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University
Xiling Du: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University
Jian Zhu: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University
Xin Xie: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: Abstract 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 both in vitro and in vivo. Our study suggests that targeting KOR might be an intriguing way to develop new MS therapies that may complement the existing immunosuppressive approaches.

Date: 2016
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DOI: 10.1038/ncomms11120

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