title: LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis.
abstract: Demyelinating diseases, such as multiple sclerosis, are characterized by the loss of the myelin sheath around neurons, owing to inflammation and gliosis in the central nervous system (CNS). Current treatments therefore target anti-inflammatory mechanisms to impede or slow disease progression. The identification of a means to enhance axon myelination would present new therapeutic approaches to inhibit and possibly reverse disease progression. Previously, LRR and Ig domain-containing, Nogo receptor-interacting protein (LINGO-1) has been identified as an in vitro and in vivo negative regulator of oligodendrocyte differentiation and myelination. Here we show that loss of LINGO-1 function by Lingo1 gene knockout or by treatment with an antibody antagonist of LINGO-1 function leads to functional recovery from experimental autoimmune encephalomyelitis. This is reflected biologically by improved axonal integrity, as confirmed by magnetic resonance diffusion tensor imaging, and by newly formed myelin sheaths, as determined by electron microscopy. Antagonism of LINGO-1 or its pathway is therefore a promising approach for the treatment of demyelinating diseases of the CNS.
authors: Biogen Idec Inc., 14 Cambridge Center, Cambridge, Massachusetts 02142, USA. sha.mi@biogenidec.com
authors: Sha
authors: S
authors: Mi
authors: Bing
authors: B
authors: Hu
authors: Kyungmin
authors: K
authors: Hahm
authors: Yi
authors: Y
authors: Luo
authors: Edward Sai
authors: ES
authors: Kam Hui
authors: Qiuju
authors: Q
authors: Yuan
authors: Wai Man
authors: WM
authors: Wong
authors: Li
authors: L
authors: Wang
authors: Huanxing
authors: H
authors: Su
authors: Tak-Ho
authors: TH
authors: Chu
authors: Jiasong
authors: J
authors: Guo
authors: Wenming
authors: W
authors: Zhang
authors: Kwok-Fai
authors: KF
authors: So
authors: Blake
authors: B
authors: Pepinsky
authors: Zhaohui
authors: Z
authors: Shao
authors: Christilyn
authors: C
authors: Graff
authors: Ellen
authors: E
authors: Garber
authors: Vincent
authors: V
authors: Jung
authors: Ed Xuekui
authors: EX
authors: Wu
authors: Wutian
authors: W
authors: Wu
mesh_terms: D000818:Animals; D001369:Axons / Q000000981:diagnostic imaging / Q000502:physiology* / Q000648:ultrastructure; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced* / Q000473:pathology; D007278:Injections, Spinal; D008565:Membrane Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D018992:Myelin-Associated Glycoprotein / Q000276:immunology / Q000494:pharmacology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D014057:Tomography, X-Ray Computed
chemical_list: C523678:LINGO1 protein, mouse; C525164:LINGO1 protein, rat; D008565:Membrane Proteins; C571327:Mog protein, mouse; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins