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
-
Transplantation of Adipose Tissue-Derived Stem Cells for Treatment of Focal Cerebral Ischemia
Current Neurovascular Research Cholecystokinin Antagonists A New Way to Improve the Analgesia from Old Analgesics?
Current Pharmaceutical Design Exploring the Mitochondrial Apoptotic Cell Death Landscape and Associated Components Serving as Molecular Targets, Primarily for Synthetic and Natural Drugs Targeting Oncology Therapeutics
Current Molecular Pharmacology Targeting Ionotropic Glutamate Receptors in the Treatment of Epilepsy
Current Neuropharmacology Neurobehavioral Evaluation in the Preterm and Term Infant
Current Pediatric Reviews Current Progress in Molecular Responses to Acidosis in the Central Nervous System
Current Medicinal Chemistry - Central Nervous System Agents Bone Regeneration and Repair
Current Stem Cell Research & Therapy The Role of Fatty Acids in the Regulation of Cerebral Vascular Function and Neuroprotection in Ischemia
CNS & Neurological Disorders - Drug Targets Benzimidazole Derivative Ameliorates Opioid-Mediated Tolerance during Anticancer- Induced Neuropathic Pain in Mice
Anti-Cancer Agents in Medicinal Chemistry Xenogeneic Decellularized Extracellular Matrix-based Biomaterials For Peripheral Nerve Repair and Regeneration
Current Neuropharmacology Dose-Response Effects of the CM11 as a Short Cationic Antimicrobial Peptide on Histopathological and Biochemical Changes in Mice
Current Chemical Biology Ketamine: New Indications for an Old Drug
Current Drug Targets Pharmacoproteomics Applications for Drug Target Discovery in CNS Disorders
Current Pharmacogenomics and Personalized Medicine Pulmonary Circulation and Pulmonary Function in Neonatal Lung Hypoplasia:Treatment with Corticosteroids
Current Pediatric Reviews Targeting ADAM12 in Human Disease: Head, Body or Tail?
Current Pharmaceutical Design The Role of Neuropeptides and Neurohormones in Neurogenic Cardiac Arrhythmias
Current Drug Targets - Cardiovascular & Hematological Disorders Cell to Cell Spreading of Misfolded Proteins as a Therapeutic Target in Motor Neuron Disease
Current Medicinal Chemistry Dual Effects of Antioxidants in Neurodegeneration: Direct Neuroprotection against Oxidative Stress and Indirect Protection via Suppression of Gliamediated Inflammation
Current Pharmaceutical Design Present Drug Therapy of Demyelinating Disorders
Current Drug Therapy Minocycline Increases in-vitro Cortical Neuronal Cell Survival after Laser Induced Axotomy
Current Clinical Pharmacology