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Spinal Cord Injury and the Neuron-Intrinsic Regeneration-Associated Gene Program

NeuroMolecular Medicine volume 16, pages 799–813 (2014)Cite this article

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.

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Acknowledgments

The authors acknowledge the editorial help of Dr. Matthew Mason.

Conflict of interest

The authors declare that they have no conflict of interest.

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Affiliations

  1. Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, an Institute of the Royal Academy of Arts and Sciences, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands

    Nitish D. Fagoe, Jessica van Heest & Joost Verhaagen

  2. Center for Neurogenomics and Cognition Research, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

    Joost Verhaagen

Authors
  1. Nitish D. Fagoe
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  2. Jessica van Heest
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  3. Joost Verhaagen
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Correspondence to Nitish D. Fagoe.

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Fagoe, N.D., van Heest, J. & Verhaagen, J. Spinal Cord Injury and the Neuron-Intrinsic Regeneration-Associated Gene Program. Neuromol Med 16, 799–813 (2014). https://doi.org/10.1007/s12017-014-8329-3

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  • DOI: https://doi.org/10.1007/s12017-014-8329-3

Keywords

  • Axon regeneration
  • Transcription factors
  • AAV
  • Spinal cord injury
  • RAG program
  • CNS