title: Spinal cord injury and the neuron-intrinsic regeneration-associated gene program.
abstract: Spinal cord injury (SCI) affects millions of people worldwide and causes a significant physical, emotional, social and economic burden. The main clinical hallmark of SCI is the permanent loss of motor, sensory and autonomic function below the level of injury. In general, neurons of the central nervous system (CNS) are incapable of regeneration, whereas injury to the peripheral nervous system is followed by axonal regeneration and usually results in some degree of functional recovery. The weak neuron-intrinsic regeneration-associated gene (RAG) response upon injury is an important reason for the failure of neurons in the CNS to regenerate an axon. This response consists of the expression of many RAGs, including regeneration-associated transcription factors (TFs). Regeneration-associated TFs are potential key regulators of the RAG program. The function of some regeneration-associated TFs has been studied in transgenic and knock-out mice and by adeno-associated viral vector-mediated overexpression in injured neurons. Here, we review these studies and propose that AAV-mediated gene delivery of combinations of regeneration-associated TFs is a potential strategy to activate the RAG program in injured CNS neurons and achieve long-distance axon regeneration.
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, an Institute of the Royal Academy of Arts and Sciences, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands, ndfagoe@gmail.com.
authors.forename: Nitish D
authors.initials: ND
authors.lastname: Fagoe
authors.forename: Jessica
authors.initials: J
authors.lastname: van Heest
authors.forename: Joost
authors.initials: J
authors.lastname: Verhaagen
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D001921:Brain / Q000502:physiology; D000229:Dependovirus / Q000235:genetics; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use; D057166:High-Throughput Screening Assays; D006655:Histone Deacetylases; D006801:Humans; D008322:Mammals / Q000502:physiology; D023421:Models, Animal; D009416:Nerve Regeneration / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D010525:Peripheral Nerves / Q000502:physiology; D020127:Recovery of Function; D013116:Spinal Cord / Q000502:physiology; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic
chemical_list: D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D006655:Histone Deacetylases