Targeting myelin to optimize plasticity of spared spinal axons.
Functional re-innervation of target neurons following neurological damage such as spinal cord injury is an essential requirement of potential therapies. There are at least two avenues by which this can be achieved: (a) through the regeneration of injured axons and (b) through promoting plasticity of those spared by the initial insult. There are several reasons why the latter approach may be more feasible, not the least of which are the inhibitory character of the glial scar, the often long distances over which injured axons must regrow, and the fact that spared axons are often already in the vicinity of denervated targets. The challenge is to unveil the well-recognized intrinsic plasticity of spared axons in a way that avoids complications, such as pain or autonomic dysfunction. One approach that we as well as others have taken is to target growth-suppressing signaling pathways initiated in spared axons by myelin-derived proteins. This article reviews models used for the study of spinal axon plasticity and describes the anatomical and behavioral effects of interfering with myelinderived proteins, their receptors, and components of their intracellular signaling cascades.
Scott
Angela L M
AL
International Collaboration on Repair Discoveries, The University of British Columbia, Vancouver, Canada.
Ramer
Leanne M
LM
Soril
Lesley J J
LJ
Kwiecien
Jacek M
JM
Ramer
Matt S
MS
D000818:Animals; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism*; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D009185:Myelin Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology
D006131:Growth Inhibitors; D009185:Myelin Proteins; D011956:Receptors, Cell Surface