Axon regeneration inhibitors.
OBJECTIVE
To increase awareness of the advancements in nerve regeneration.


METHODS
Review of the literature regarding inhibitors of nerve outgrowth and presentation of potential agents that reverse the inhibition, thereby promoting nerve regeneration.


RESULTS
The injured adult central nervous system (CNS) inhibits axon outgrowth, thereby limiting recovery from traumatic injury. Axon regeneration inhibitors (ARIs) that contribute to inhibition of recovery include myelin-associated glycoprotein, Nogo, oligodendrocyte-myelin glycoprotein and chondroitin sulfate proteoglycans. The ARIs bind to specific receptors on the axon growth cone to halt outgrowth; consequently, reversing or blocking the actions of ARIs may promote recovery after CNS injury. Sialidase, an enzyme that cleaves one class of axonal receptors for myelin-associated glycoprotein, enhances spinal axon outgrowth into implanted peripheral nerve grafts in a rat model of brachial plexus avulsion, a traumatic injury in which nerve roots are torn from the spinal cord.


CONCLUSIONS
Repair using peripheral nerve grafts is a promising restorative surgical treatment in humans, although functional improvement remains limited. Molecular therapies targeting ARIs may aid functional recovery after brachial plexus avulsion or other nervous system injuries and diseases.
Yang
Lynda J-S
LJ
Department of Neurosurgery, University of Michigan Health System, Ann Arbor, MI 48109-5338, USA. ljsyang@med.umich.edu
Schnaar
Ronald L
RL
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000627:therapeutic use; D008565:Membrane Proteins / Q000627:therapeutic use; D008954:Models, Biological; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology*; D009439:Neuraminidase / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000628:therapy*
C475168:CHODL protein, human; D037181:Lectins, C-Type; D008565:Membrane Proteins; D018992:Myelin-Associated Glycoprotein; D009439:Neuraminidase