Axon growth inhibition by RhoA/ROCK in the central nervous system

Frontiers in Neuroscience, 2014 · DOI: 10.3389/fnins.2014.00338 · Published: October 22, 2014

Regenerative Medicine Neurology Genetics

Simple Explanation

The RhoA/ROCK pathway is associated with various neuronal functions such as migration, dendrite development, and axonal extension. The RhoA/ROCK pathway mediates the effects of myelin-associated axon growth inhibitors—Nogo, myelin-associated glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp), and repulsive guidance molecule (RGM). Blocking RhoA/ROCK signaling can reverse the inhibitory effects of these molecules on axon outgrowth, and promotes axonal sprouting and functional recovery in animal models of CNS injury.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
RhoA/ROCK signaling is involved in various central nervous system (CNS) diseases, including optic nerve and spinal cord injuries, stroke, and neurodegenerative diseases.
2
Multiple axon growth inhibitory molecules converge on RhoA/ROCK in neurons.
3
The ROCK inhibitor Y-27632 attenuates the inhibitory effect of these myelin-associated inhibitors.

Research Summary

Rho kinase (ROCK) is a serine/threonine kinase and a downstream target of the small GTPase Rho. The RhoA/ROCK pathway is associated with various neuronal functions such as migration, dendrite development, and axonal extension. Blocking RhoA/ROCK signaling can reverse the inhibitory effects of these molecules on axon outgrowth, and promotes axonal sprouting and functional recovery in animal models of CNS injury.

Practical Implications

Therapeutic Target

The RhoA/ROCK pathway is a potential therapeutic target for CNS diseases.

Drug Development

Development of therapeutic agents targeting the RhoA/ROCK pathway is expected to contribute to the treatment of CNS diseases.

Clinical trials

Several RhoA/ROCK inhibitors have been under development or in clinical trials as therapeutic agents for neurological disorders.

Study Limitations

1
Timing of administration of RhoA/ROCK inhibitors needs to be discussed in more detail.
2
Low drug selectivity of some RhoA/ROCK inhibitors needs to be addressed.
3
Unresolved problems should be addressed to achieve the therapeutic applications of RhoA/ROCK inhibitors.

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