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Rho Kinase Inhibition Enhances Axonal Regeneration in the Injured CNS
Open accessAbstract
Myelin-associated inhibitors limit axonal regeneration in the injured brain and spinal cord. A common target of many neurite outgrowth inhibitors is the Rho family of small GTPases. Activation of Rho and a downstream effector of Rho, p160ROCK, inhibits neurite outgrowth. Here, we demonstrate that Rho is directly activated by the myelin-associated inhibitor Nogo-66. Using a binding assay to measure Rho activity, we detected increased levels of GTP Rho in PC12 and dorsal root ganglion (DRG) cell lysates after Nogo-66 stimulation. Rho activity levels were not affected by Amino-Nogo stimulation. Rho inactivation with C3 transferase promotes neurite outgrowth of chick DRG neurons in vitro, but with the delivery method used here, it fails to promote neurite outgrowth after corticospinal tract (CST) lesions in the adult rat. Inhibition of p160ROCK with Y-27632 also promotes neurite outgrowth on myelin-associated inhibitors in vitro. Furthermore, Y-27632 enhances sprouting of CST fibers in vivo and accelerates locomotor recovery after CST lesions in adult rats.
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Cites
Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase
Amano, M., Chihara, K., Kimura, K., Fukata, Y., Nakamura, N., Matsuura, Y., & Kaibuchi, K. (1997) · Science · doi:10.1126/science.275.5304.1308 · Cited by 1,077
Cited by
Glial inhibition of CNS axon regeneration
Yiu, G., & He, Z. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1956 · Cited by 1,495
Therapeutic interventions after spinal cord injury
Thuret, S., Moon, L. D. F., & Gage, F. H. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1955 · Cited by 1,012
Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS
Filbin, M. T. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1195 · Cited by 871
Schwab, M. E. (2004) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2004.01.004 · Cited by 613
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
Metadata
- Authors
- Fournier, A. E., Takizawa, B. T., & Strittmatter, S. M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-02-15
- Volume
- 23
- Issue
- 4
- Pages
- 1416-1423
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W1940297232
- Cited by
- 644
- References
- 1
- FWCI
- 14.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Fournier, A. E., Takizawa, B. T., & Strittmatter, S. M. (2003). Rho Kinase Inhibition Enhances Axonal Regeneration in the Injured CNS. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.23-04-01416.2003
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
