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Rho Signaling Pathway Targeted to Promote Spinal Cord Repair
Open accessAbstract
The Rho signaling pathway regulates the cytoskeleton and motility and plays an important role in neuronal growth inhibition. Here we demonstrate that inactivation of Rho or its downstream target Rho-associated kinase (ROK) stimulated neurite growth in primary cells of cortical neurons plated on myelin or chondroitin sulfate proteoglycan substrates. Furthermore, treatment either with C3 transferase (C3) to inactivate Rho or with Y27632 to inhibit ROK was sufficient to stimulate axon regeneration and recovery of hindlimb function after spinal cord injury (SCI) in adult mice. Injured mice were treated with a single injection of Rho or Rho-associated kinase inhibitors delivered in a protein adhesive at the lesion site. Treated animals showed long-distance regeneration of anterogradely labeled corticospinal axons and increased levels of GAP-43 mRNA in the motor cortex. Behaviorally, inactivation of Rho pathway induced rapid recovery of locomotion and progressive recuperation of forelimb-hindlimb coordination. These findings provide evidence that the Rho signaling pathway is a potential target for therapeutic interventions after spinal cord injury.
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Cites
Davies, S. J. A., Goucher, D. R., Doller, C., & Silver, J. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-14-05810.1999 · Cited by 606
Cited by
Ahuja, C. S., Wilson, J. R., Nori, S., Kotter, M. R. N., Druschel, C., Curt, A., & Fehlings, M. G. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.18 · Cited by 2,441
ROCKs: multifunctional kinases in cell behaviour
Riento, K., & Ridley, A. J. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1128 · Cited by 1,941
The bright side of the glial scar in CNS repair
Rolls, A., Shechter, R., & Schwartz, M. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2591 · Cited by 674
Rho kinase, a promising drug target for neurological disorders
Mueller, B. K., Mack, H., & Teusch, N. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1719 · Cited by 608
Spinal shock revisited: a four-phase model
Ditunno, J. F., Little, J. W., Tessler, A., & Burns, A. S. (2004) · Spinal Cord · doi:10.1038/sj.sc.3101603 · Cited by 441
Metadata
- Authors
- Dergham, P., Ellezam, B., Essagian, C., Avedissian, H., Lubell, W. D., & McKerracher, L.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-08-01
- Volume
- 22
- Issue
- 15
- Pages
- 6570-6577
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2104907082
- Cited by
- 726
- References
- 1
- FWCI
- 26.22
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Dergham, P., Ellezam, B., Essagian, C., Avedissian, H., Lubell, W. D., & McKerracher, L. (2002). Rho Signaling Pathway Targeted to Promote Spinal Cord Repair. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.22-15-06570.2002
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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