title: Regulating Axonal Responses to Injury: The Intersection between Signaling Pathways Involved in Axon Myelination and The Inhibition of Axon Regeneration.
abstract: Following spinal cord injury (SCI), a multitude of intrinsic and extrinsic factors adversely affect the gene programs that govern the expression of regeneration-associated genes (RAGs) and the production of a diversity of extracellular matrix molecules (ECM). Insufficient RAG expression in the injured neuron and the presence of inhibitory ECM at the lesion, leads to structural alterations in the axon that perturb the growth machinery, or form an extraneous barrier to axonal regeneration, respectively. Here, the role of myelin, both intact and debris, in antagonizing axon regeneration has been the focus of numerous investigations. These studies have employed antagonizing antibodies and knockout animals to examine how the growth cone of the re-growing axon responds to the presence of myelin and myelin-associated inhibitors (MAIs) within the lesion environment and caudal spinal cord. However, less attention has been placed on how the myelination of the axon after SCI, whether by endogenous glia or exogenously implanted glia, may alter axon regeneration. Here, we examine the intersection between intracellular signaling pathways in neurons and glia that are involved in axon myelination and axon growth, to provide greater insight into how interrogating this complex network of molecular interactions may lead to new therapeutics targeting SCI.
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine Miami, FL, USA.
authors.forename: Sudheendra N R
authors.initials: SN
authors.lastname: Rao
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of MedicineMiami, FL, USA; The Department of Neurological Surgery, University of Miami Miller School of MedicineMiami, FL, USA; The Neuroscience Program, University of Miami Miller School of MedicineMiami, FL, USA; The Interdisciplinary Stem Cell Institute, University of Miami Miller School of MedicineMiami, FL, USA; Bruce W. Carter Department of Veterans Affairs Medical CenterMiami, FL, USA.
authors.forename: Damien D
authors.initials: DD
authors.lastname: Pearse
keywords: Schwann cell; adaptive myelination; axon regeneration; myelination; oligodendrocytes; radial growth; signaling pathways; spinal cord injuries