Myelin-Associated Inhibitors in Axonal Growth after Central Nervous System Injury
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2015. Elsevier Inc. All rights reserved. A major hypothesis for the limited axon regeneration in the injured central nervous system (CNS) is the presence of axon growth inhibitors associated with CNS myelin. Extensive biochemical and cell culture studies have yielded a wealth of information on the molecular identity and signaling network of myelin-associated axon growth inhibitors and their neuronal receptors. Significant effort has been made to delineate their roles in injury-induced axonal growth in vivo, including the regeneration of injured axons and the compensatory sprouting of uninjured axons. There is strong evidence that myelin inhibitors modulate axon sprouting, a form of CNS's innate repair process, albeit in unexpectedly complex ways. Meanwhile, axon regeneration remains limited by targeting myelin inhibitors alone and their function in regeneration may depend on other factors such as an elevated level of neuron-intrinsic growth capacity. In addition to the prototypical myelin inhibitors Nogo, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein, several axon guidance molecules have been proposed to serve similar functions. Understanding the in vivo role of myelin inhibitors in axon sprouting and regeneration along with their interplay with other axon growth regulators remains an important challenge for CNS injury and repair research.
