title: Blockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting and recovery after spinal injury.
abstract: The growth of injured axons in the adult mammalian CNS is limited after injury. Three myelin proteins, Nogo, MAG (myelin-associated glycoprotein), and OMgp (oligodendrocyte myelin glycoprotein), bind to the Nogo-66 receptor (NgR) and inhibit axonal growth in vitro. Transgenic or viral blockade of NgR function allows axonal sprouting in vivo. Here, we administered the soluble function-blocking NgR ectodomain [aa 27-310; NgR(310)ecto] to spinal-injured rats. Purified NgR(310)ecto-Fc protein was delivered intrathecally after midthoracic dorsal over-hemisection. Axonal sprouting of corticospinal and raphespinal fibers in NgR(310)ecto-Fc-treated animals correlates with improved spinal cord electrical conduction and improved locomotion. The ability of soluble NgR(310)ecto to promote axon growth and locomotor recovery demonstrates a therapeutic potential for NgR antagonism in traumatic spinal cord injury.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Shuxin
authors.initials: S
authors.lastname: Li
authors.forename: Betty P
authors.initials: BP
authors.lastname: Liu
authors.forename: Stephane
authors.initials: S
authors.lastname: Budel
authors.forename: Mingwei
authors.initials: M
authors.lastname: Li
authors.forename: Benxiu
authors.initials: B
authors.lastname: Ji
authors.forename: Lee
authors.initials: L
authors.lastname: Walus
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.forename: Adrienna
authors.initials: A
authors.lastname: Jirik
authors.forename: Sylvia
authors.initials: S
authors.lastname: Rabacchi
authors.forename: Eugene
authors.initials: E
authors.lastname: Choi
authors.forename: Dane
authors.initials: D
authors.lastname: Worley
authors.forename: Dinah W Y
authors.initials: DW
authors.lastname: Sah
authors.forename: Blake
authors.initials: B
authors.lastname: Pepinsky
authors.forename: Daniel
authors.initials: D
authors.lastname: Lee
authors.forename: Jane
authors.initials: J
authors.lastname: Relton
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strittmatter
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D019054:Evoked Potentials, Motor; D005260:Female; D058851:GPI-Linked Proteins; D007278:Injections, Spinal; D009043:Motor Activity; D009185:Myelin Proteins / Q000037:antagonists & inhibitors*; D018992:Myelin-Associated Glycoprotein / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D063308:Myelin-Oligodendrocyte Glycoprotein; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D009836:Oligodendroglia / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D012995:Solubility; D013116:Spinal Cord / Q000503:physiopathology / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D058851:GPI-Linked Proteins; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; C495858:NgR(310) Ecto-Fc protein; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; C560532:Omg protein, rat; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; C000603197:Rtn4 protein, rat; C486581:Rtn4r protein, rat; D012701:Serotonin