The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar

@article{Monnier2003TheRP,
  title={The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar},
  author={Philippe P. Monnier and Ana Sierra and Jan M. Schwab and Sigrid Henke-Fahle and Bernhard K. Mueller},
  journal={Molecular and Cellular Neuroscience},
  year={2003},
  volume={22},
  pages={319-330}
}
Role of Rho kinase pathway in chondroitin sulfate proteoglycan‐mediated inhibition of neurite outgrowth in PC12 cells
TLDR
The data demonstrate that the interaction of CSPG with the ROCK pathway involves downstream effectors of ROCK such as myosin phosphatase and cofilin, and is noncompetitive in nature.
Modulation of Rho GTPase activity alleviates chondroitin sulfate proteoglycan‐dependent inhibition of neurite extension
TLDR
Activation of Cdc42 and Rac, as well as inhibition of Rho, helps overcome the CSPG‐dependent inhibition of neurite extension and shows that these mutant proteins require the delivery vehicle, Chariot, to enter the neurons and affect neurite Extension.
Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo
TLDR
It is demonstrated that inhibition of ROCK can be an effective therapeutic approach to increase regeneration of CNS neurons and to minimize unwanted side effects and to avoid deleterious effects on nerve fiber growth.
Intra-Axonal Translation of RhoA Promotes Axon Growth Inhibition by CSPG
TLDR
It is shown that axonal growth inhibition mediated by C SPGs requires intra-axonal protein synthesis and that local translation of RhoA contributes to the axon growth inhibitory effect of CSPGs.
ROCK inhibition with Y27632 activates astrocytes and increases their expression of neurite growth‐inhibitory chondroitin sulfate proteoglycans
TLDR
Increased expression of inhibitory CSPGs in the ECM of the glial scar may counteract the growth promoting effects of ROCK inhibition on axonal growth cones, and support a model where ROCK inhibition by Y27632 modifies astrocytic processing of C SPGs, and increases the presence of CSPG within the ECm while reduces CSPGS in the CM.
Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation
TLDR
It is hypothesized that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site, and CS-impaired cell migration in vitro induced the formation of large mature adhesions and altered cell protrusion dynamics.
Proteoglycans and injury of the central nervous system
TLDR
It is suggested that chondroitin sulfate proteoglycans (CSPG) are responsible for unsuccessful axonal regeneration in glial scars, and the most effective combination of these treatments needs to be examined in the future.
The Pivotal Role of RhoA GTPase in the Molecular Signaling of Axon Growth Inhibition after CNS Injury and Targeted Therapeutic Strategies
TLDR
Several critical points of convergence within the developing or regenerating neuron for mediating intracellular cell signaling effects on the growth cone cytoskeleton have been identified, and their modulation has produced marked increases in axon outgrowth within the “nonpermissive” milieu of the adult injured CNS.
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TLDR
In this model of gliosis, particular PGs may act as inhibitors of neurite outgrowth by attenuating the potential for axon elongation that could occur due to the concomitant expression of growth-promoting molecules in regions of reactive gliosis.
Bovine CNS Myelin Contains Neurite Growth-Inhibitory Activity Associated with Chondroitin Sulfate Proteoglycans
TLDR
The results strongly suggest that brevican and versican V2 are additional components of CNS myelin that contribute to its nonpermissive substrate properties for axonal growth.
Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes
TLDR
The inability of the adult glial scar tissue to support neurite outgrowth was best correlated with the expression of CS-PG and CT, suggesting that these molecules may be involved in limiting the growth of regenerating axons in the CNS after injury.
Degradation of Chondroitin Sulfate Proteoglycan Enhances the Neurite-Promoting Potential of Spinal Cord Tissue
TLDR
Observed increases in neurite outgrowth on chondroitinase-treated tissues were largely inhibited in the presence of function-blocking laminin antibodies, indicating that inhibitory CSPG is widely distributed and predominant in both normal and injured spinal cord tissues.
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TLDR
Detailed analysis of the morphology and behavior of sensory neurons, and a human nerve cell model, as they contacted nervous system–derived CSPGs are analyzed, showing for the first time the ultrastructure of sensory growth cones at a CSPG‐laminin border and revealing details of growth cone and neurite organization at this choice point.
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TLDR
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TLDR
It is shown that the CSPG neurocan, which is expressed in the CNS, exerts a repulsive effect on growing cerebellar axons and raises the possibility that neurocan interferes with axonal regeneration after CNS injury.
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TLDR
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Myelin-associated inhibitors of neurite growth and regeneration in the CNS
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