Blockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting and recovery after spinal injury.
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.
Li
Shuxin
S
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Liu
Betty P
BP
Budel
Stephane
S
Li
Mingwei
M
Ji
Benxiu
B
Walus
Lee
L
Li
Weiwei
W
Jirik
Adrienna
A
Rabacchi
Sylvia
S
Choi
Eugene
E
Worley
Dane
D
Sah
Dinah W Y
DW
Pepinsky
Blake
B
Lee
Daniel
D
Relton
Jane
J
Strittmatter
Stephen M
SM
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
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