Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo
Abstract
Inhibitory molecules derived from CNS myelin and glial scar tissue are major causes for insufficient functional regeneration in the mammalian CNS. A multitude of these molecules signal through the Rho/Rho kinase (ROCK) pathway. We evaluated three inhibitors of ROCK, Y- 27632, Fasudil (HA-1077), and Dimethylfasudil (H-1152), in models of neurite outgrowth in vitro. We show, that all three ROCK inhibitors partially restore neurite outgrowth of Ntera-2 neurons on the inhibitory chondroitin sulphate proteoglycan substrate. In the rat optic nerve crush model Y-27632 dose-dependently increased regeneration of retinal ganglion cell axons in vivo. Application of Dimethylfasudil showed a trend towards increased axonal regeneration in an intermediate concentration. We demonstrate that inhibition of ROCK can be an effective therapeutic approach to increase regeneration of CNS neurons. The selection of a suitable inhibitor with a broad therapeutic window, however, is crucial in order to minimize unwanted side effects and to avoid deleterious effects on nerve fiber growth.
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RhoA integrates molecular signals to organize sophisticated and coordinated variations in gene expression and actin cytoskeleton, crucial processes for neurite outgrowth and synaptic connectivity.
“It integrates molecular signals to organize sophisticated and coordinated variations in gene expression and actin cytoskeleton, crucial processes for the neurite outgrowth and synaptic connectivity [53,54].”
From Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome (2022) · cites this paper as [53]
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- Authors
- Lingor, P., Teusch, N., Schwarz, K., Mueller, R., Mack, H., Bähr, M., & Mueller, B. K.
- Affiliations
- University of Göttingen (DE)
- Abbott (Germany) (DE)
- Corresponding author
- Bähr, Mathias
- Mueller, Bernhard K.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-06-09
- Volume
- 103
- Issue
- 1
- Pages
- 181-189
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2011497398
- Cited by
- 214
- References
- 37
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 13 · 2021: 5 · 2020: 14 · 2019: 9 · 2018: 15 · 2017: 10 · 2016: 17 · 2015: 15 · 2014: 23 · 2013: 17 · 2012: 14
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- GRO (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- Rho kinase inhibition, ROCK inhibitor, neurite outgrowth, chondroitin sulfate proteoglycans, axon regeneration, optic nerve crush, retinal ganglion cells, Y-27632, fasudil, glial scar, central nervous system regeneration
- MeSH terms
- Amides, Animals, Axons, Cell Line, Dose-Response Relationship, Drug, Enzyme Inhibitors, Female, Humans, Nerve Crush, Nerve Regeneration, Neurons, Optic Nerve, Chondroitin Sulfate Proteoglycans, Pyridines, Neurites, Rats, Wistar, Protein Serine-Threonine Kinases, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Optic Nerve Injuries, Intracellular Signaling Peptides and Proteins, Rats, rho-Associated Kinases
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