title: Kappa opioid receptor activation alleviates experimental autoimmune encephalomyelitis and promotes oligodendrocyte-mediated remyelination.
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.
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Du
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Yanhui
authors.identifier: http://orcid.org/0000-0002-3009-3506
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Cai
authors.affiliation: CAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chai
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lv
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Xiling
authors.initials: X
authors.lastname: Du
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-Medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.|CAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000627:therapeutic use; D000081:Acetamides / Q000627:therapeutic use; D000818:Animals; D002454:Cell Differentiation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011759:Pyrrolidines / Q000627:therapeutic use; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism / Q000502:physiology*
chemical_list: D000081:Acetamides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C092095:asimadoline