About this Research Topic
In honour of the life and work of Dr. Marie T. Filbin (1955-2014), we call on contributors to submit original research articles and reviews on the subject of myelin-mediated inhibition of axonal growth in the central nervous system. Through these articles, we hope to highlight past achievements in the field, novel findings from current studies, and innovative ideas that will lead to new advances in the treatment of spinal cord injury.
Pioneering studies conducted in the 1980’s laid the foundation for the hypothesis that axonal regeneration is limited by CNS myelin, and the identification of myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte myelin glycoprotein (OMgp) as inhibitors of neurite outgrowth firmly established myelin as a key factor in regenerative failure. Mechanistically, it has been shown that MAG, Nogo, and OMgp mediate inhibition by binding to either Nogo receptor (NgR) or paired immunoglobulin receptor B (PirB), and initiating a signaling cascade that culminates in the activation of RhoA. We encourage our colleagues to offer their perspectives on these established mechanisms, and present their latest findings related to myelin-associated inhibitors, receptors, and signaling pathways.
Since the discovery of these proteins, there has been tremendous interest in identifying compounds and molecular mechanisms that are capable of overcoming myelin-mediated inhibition. Many studies have focused on pharmacological antagonism of receptors and signaling intermediates, while others have sought to identify and enhance endogenous pro-regenerative pathways. The most notable example of the latter is the conditioning lesion effect, which led to the discovery of cyclic AMP’s ability to overcome inhibition by MAG and myelin. Many of the agents tested in these studies have been shown to promote axonal regeneration in vivo, and this research topic will provide a platform for researchers to share information about new treatments that have been developed in both academia and industry. We also welcome discussions of commonly used injury models, such as optic nerve crush, dorsal column lesion, and spinal cord contusion, and descriptions of new techniques for assessing axonal regeneration.
As we look toward the future, it is becoming increasingly clear that reversal of myelin-mediated inhibition alone will not be sufficient to produce functional recovery from spinal cord injury, and that other factors, such as astroglial scarring, the expression of chondroitin sulfate proteoglycans, neuronal cell death, and lack of neurotrophic support, must also be taken into consideration. Combinatorial approaches therefore hold a great deal of promise, and we hope to initiate a dialogue on how stem cell transplantation, chondroitinase ABC, gene therapy, growth-promoting agents such as rolipram, and other methods can be combined to optimize functional recovery. We also encourage clinician-scientists to comment on the translational aspects of these approaches, particularly with regard to the design and implementation of clinical trials.
Pioneering studies conducted in the 1980’s laid the foundation for the hypothesis that axonal regeneration is limited by CNS myelin, and the identification of myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte myelin glycoprotein (OMgp) as inhibitors of neurite outgrowth firmly established myelin as a key factor in regenerative failure. Mechanistically, it has been shown that MAG, Nogo, and OMgp mediate inhibition by binding to either Nogo receptor (NgR) or paired immunoglobulin receptor B (PirB), and initiating a signaling cascade that culminates in the activation of RhoA. We encourage our colleagues to offer their perspectives on these established mechanisms, and present their latest findings related to myelin-associated inhibitors, receptors, and signaling pathways.
Since the discovery of these proteins, there has been tremendous interest in identifying compounds and molecular mechanisms that are capable of overcoming myelin-mediated inhibition. Many studies have focused on pharmacological antagonism of receptors and signaling intermediates, while others have sought to identify and enhance endogenous pro-regenerative pathways. The most notable example of the latter is the conditioning lesion effect, which led to the discovery of cyclic AMP’s ability to overcome inhibition by MAG and myelin. Many of the agents tested in these studies have been shown to promote axonal regeneration in vivo, and this research topic will provide a platform for researchers to share information about new treatments that have been developed in both academia and industry. We also welcome discussions of commonly used injury models, such as optic nerve crush, dorsal column lesion, and spinal cord contusion, and descriptions of new techniques for assessing axonal regeneration.
As we look toward the future, it is becoming increasingly clear that reversal of myelin-mediated inhibition alone will not be sufficient to produce functional recovery from spinal cord injury, and that other factors, such as astroglial scarring, the expression of chondroitin sulfate proteoglycans, neuronal cell death, and lack of neurotrophic support, must also be taken into consideration. Combinatorial approaches therefore hold a great deal of promise, and we hope to initiate a dialogue on how stem cell transplantation, chondroitinase ABC, gene therapy, growth-promoting agents such as rolipram, and other methods can be combined to optimize functional recovery. We also encourage clinician-scientists to comment on the translational aspects of these approaches, particularly with regard to the design and implementation of clinical trials.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
