Abstract
After injury to the central nervous system (CNS) of adult vertebrates, axonal regeneration is extremely limited because inhibitory proteins existing around the injury site prevent the regrowth of the lesioned axons. Previous studies have reported that several myelin-derived proteins (such as Nogo, MAG, OMgp) and developmental guidance proteins (such as RGM, semaphorin, ephrin) contribute to the inhibition of axonal regeneration after injury in the adult CNS. Although each neurite growth inhibitory protein induces neurite retraction and growth cone collapse through specific receptors, they commonly utilize the function of small GTPases, including Rho, Rac, Cdc42, and Ras, that regulate neurite outgrowth by controlling actin and microtubule cytoskeleton. The small GTPase Rho and its effector Rho-kinase play critical roles in the induction of neurite retraction and growth cone collapse in vitro and the inhibition of axonal regeneration in vivo. Therefore, the Rho inhibitor C3 transferase and Rho-kinase inhibitors are thought to be effective therapeutic candidates involved in the promotion of axonal regeneration after human CNS injuries such as spinal cord injury.
Keywords: Small GTPase, Rho, Rho-kinase, actin, microtubule, CNS injury, axonal regeneration
Central Nervous System Agents in Medicinal Chemistry
Title: Inhibition of Rho/Rho-Kinase as Therapeutic Strategy to Promote CNS Axonal Regeneration
Volume: 7 Issue: 4
Author(s): Mitsuharu Endo and Toshihide Yamashita
Affiliation:
Keywords: Small GTPase, Rho, Rho-kinase, actin, microtubule, CNS injury, axonal regeneration
Abstract: After injury to the central nervous system (CNS) of adult vertebrates, axonal regeneration is extremely limited because inhibitory proteins existing around the injury site prevent the regrowth of the lesioned axons. Previous studies have reported that several myelin-derived proteins (such as Nogo, MAG, OMgp) and developmental guidance proteins (such as RGM, semaphorin, ephrin) contribute to the inhibition of axonal regeneration after injury in the adult CNS. Although each neurite growth inhibitory protein induces neurite retraction and growth cone collapse through specific receptors, they commonly utilize the function of small GTPases, including Rho, Rac, Cdc42, and Ras, that regulate neurite outgrowth by controlling actin and microtubule cytoskeleton. The small GTPase Rho and its effector Rho-kinase play critical roles in the induction of neurite retraction and growth cone collapse in vitro and the inhibition of axonal regeneration in vivo. Therefore, the Rho inhibitor C3 transferase and Rho-kinase inhibitors are thought to be effective therapeutic candidates involved in the promotion of axonal regeneration after human CNS injuries such as spinal cord injury.
Export Options
About this article
Cite this article as:
Endo Mitsuharu and Yamashita Toshihide, Inhibition of Rho/Rho-Kinase as Therapeutic Strategy to Promote CNS Axonal Regeneration, Central Nervous System Agents in Medicinal Chemistry 2007; 7 (4) . https://dx.doi.org/10.2174/187152407783220788
DOI https://dx.doi.org/10.2174/187152407783220788 |
Print ISSN 1871-5249 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6166 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Injection Time-Dependent Effect of Adult Human Bone Marrow Stromal Cell Transplantation in a Rat Model of Severe Traumatic Brain Injury
Current Stem Cell Research & Therapy Cytokines in the Central Nervous System: Targets for Therapeutic Intervention
Current Drug Targets - CNS & Neurological Disorders Optogenetics of the Spinal Cord: Use of Channelrhodopsin Proteins for Interrogation of Spinal Cord Circuits
Current Protein & Peptide Science Induced Pluripotent Stem Cells as a Model for Therapy Personalization of Pediatric Patients: Disease Modeling and Drug Adverse Effects Prevention
Current Medicinal Chemistry Non-transfusion Dependent Thalassemias: A Developing Country Perspective
Current Pediatric Reviews Repulsive Guidance Molecules (RGMs) and Their Potential Implication in Cancer as Co-receptor of BMPs
Current Signal Transduction Therapy Involvement of the Sodium Channel Nav1.7 in Paclitaxel-induced Peripheral Neuropathy through ERK1/2 Signaling in Rats
Current Neurovascular Research Compartmentalized Platforms for Neuro-Pharmacological Research
Current Neuropharmacology Expression of Opioid Receptors During Peripheral Inflammation
Current Topics in Medicinal Chemistry Targeting the Nogo Receptor Complex in Diseases of the Central Nervous System
Current Medicinal Chemistry Conference Report: Summary Report of the International Association of Neurorestoratology VII Conference: Regulations, Ethics, Science, and the Need of Patients Care in Neurorestoratology
CNS & Neurological Disorders - Drug Targets Neuronal Semaphorins Regulate a Primary Immune Response
Current Neurovascular Research Eph/ephrin Signaling as a Potential Therapeutic Target After Central Nervous System Injury
Current Pharmaceutical Design Advancing Drug Therapy for Brain Tumours: A Current Review of the Pro-inflammatory Peptide Substance P and its Antagonists as Anti-cancer Agents
Recent Patents on CNS Drug Discovery (Discontinued) Subtype-Selective Noncompetitive Modulators of Metabotropic Glutamate Receptor Subtype 1 (mGluR1)
Current Topics in Medicinal Chemistry Limiting Functional Deficiency Following Stroke: Exploiting Different Stem Cell Reservoirs
Current Neuropharmacology Small Peptide and Protein-based Molecular Probes for Imaging Neurological Diseases
Current Protein & Peptide Science Bruton's Tyrosine Kinase Inhibition in the Treatment of Preclinical Models and Multiple Sclerosis
Current Pharmaceutical Design Motor and Sensory Dysfunction in Musician's Dystonia
Current Neuropharmacology A Stress Repair Mechanism That Maintains Vertebrate Structure During Stress
Cardiovascular & Hematological Disorders-Drug Targets