Abstract
Functional recovery following acute CNS injury in humans, such as spinal cord injury and stroke, is exceptionally limited, leaving the affected individual with life-long neurological deficits such as loss of limb movement and sensation leading to a compromised quality of life. As yet, there is no effective treatment on the market for such injuries. This lack of functional recovery can at least in part be attributed to the restriction of axonal regeneration and neuroplasticity by several CNS myelin proteins that have been shown to be potent inhibitors of neurite outgrowth in vitro, namely myelin-associated glycoprotein (MAG), Nogo-A and oligodendrocyte myelin glycoprotein (OMgp). Nogo-A contains multiple neurite outgrowth inhibitory domains exposed on the surface of myelinating oligodendrocytes located within its amino-terminal region (amino-Nogo-A) and C-terminal region (Nogo-66). Although structurally dissimilar; Nogo-66, MAG and OMgp exert their inhibitory effects by binding the GPI-linked neuronal Nogo-66 receptor (NgR) that transduces the inhibitory signal to the cell interior via transmembrane co-receptors LINGO-1 and p75NTR or TROY. Although the receptor(s) for amino- Nogo-A are unknown, amino-Nogo-A and NgR ligands mutually activate the small GTPase RhoA. Consistent with their neurite outgrowth inhibitory function, approaches counter-acting Nogo-A using function-blocking antibodies, NgR using peptide antagonists and receptor bodies or RhoA using deactivating enzymes have been shown to significantly enhance axonal regeneration and neuroplasticity leading to improved functional recovery in animal models of acute CNS injury. These in vivo findings thus provide a sound basis for the development of an effective treatment for acute CNS injuries in humans.
Keywords: Acute CNS injury, antibodies, axonal regeneration, myelin, neuroplasticity, Nogo-A, Nogo-66 receptor
Current Pharmaceutical Design
Title: Targeting the Nogo-A Signalling Pathway to Promote Recovery Following Acute CNS Injury
Volume: 13 Issue: 24
Author(s): A. R. Walmsley and A. K. Mir
Affiliation:
Keywords: Acute CNS injury, antibodies, axonal regeneration, myelin, neuroplasticity, Nogo-A, Nogo-66 receptor
Abstract: Functional recovery following acute CNS injury in humans, such as spinal cord injury and stroke, is exceptionally limited, leaving the affected individual with life-long neurological deficits such as loss of limb movement and sensation leading to a compromised quality of life. As yet, there is no effective treatment on the market for such injuries. This lack of functional recovery can at least in part be attributed to the restriction of axonal regeneration and neuroplasticity by several CNS myelin proteins that have been shown to be potent inhibitors of neurite outgrowth in vitro, namely myelin-associated glycoprotein (MAG), Nogo-A and oligodendrocyte myelin glycoprotein (OMgp). Nogo-A contains multiple neurite outgrowth inhibitory domains exposed on the surface of myelinating oligodendrocytes located within its amino-terminal region (amino-Nogo-A) and C-terminal region (Nogo-66). Although structurally dissimilar; Nogo-66, MAG and OMgp exert their inhibitory effects by binding the GPI-linked neuronal Nogo-66 receptor (NgR) that transduces the inhibitory signal to the cell interior via transmembrane co-receptors LINGO-1 and p75NTR or TROY. Although the receptor(s) for amino- Nogo-A are unknown, amino-Nogo-A and NgR ligands mutually activate the small GTPase RhoA. Consistent with their neurite outgrowth inhibitory function, approaches counter-acting Nogo-A using function-blocking antibodies, NgR using peptide antagonists and receptor bodies or RhoA using deactivating enzymes have been shown to significantly enhance axonal regeneration and neuroplasticity leading to improved functional recovery in animal models of acute CNS injury. These in vivo findings thus provide a sound basis for the development of an effective treatment for acute CNS injuries in humans.
Export Options
About this article
Cite this article as:
A. R. Walmsley and A. K. Mir , Targeting the Nogo-A Signalling Pathway to Promote Recovery Following Acute CNS Injury, Current Pharmaceutical Design 2007; 13 (24) . https://dx.doi.org/10.2174/138161207781368611
DOI https://dx.doi.org/10.2174/138161207781368611 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- 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
-
Role of Sirtuins and Calorie Restriction in Neuroprotection: Implications in Alzheimers and Parkinsons Diseases
Current Pharmaceutical Design Glycosphingolipid Structure and Function in Membranes
Current Organic Chemistry Glutamatergic Neurotransmission As Molecular Target of New Anticonvulsants
Current Topics in Medicinal Chemistry The Development of Hyaluronic Acids Used for Skin Tissue Regeneration
Current Drug Delivery Antagonists of the Vasopressin V1 Receptor and of the β<sub>1</sub>-Adrenoceptor Inhibit Cytotoxic Brain Edema in Stroke by Effects on Astrocytes-but the Mechanisms Differ
Current Neuropharmacology An Improved and Validated HPLC Method for the Determination of Methylprednisolone Sodium Succinate and its Degradation Products in Nanoparticles
Current Pharmaceutical Analysis Mesenchymal Stem Cell Research in Veterinary Medicine
Current Stem Cell Research & Therapy Antioxidant Activity of Galantamine and Some of its Derivatives
Current Medicinal Chemistry Voltage-Gated Calcium Channels as Targets for the Treatment of Chronic Pain
Current Drug Targets - CNS & Neurological Disorders Advances in Stem Cells Transplantation for the Therapy of Parkinson’s Disease
Current Stem Cell Research & Therapy The Multifunctional Mesencephalic Locomotor Region
Current Pharmaceutical Design Targeting TNF-Alpha to Elucidate and Ameliorate Neuroinflammation in Neurodegenerative Diseases
CNS & Neurological Disorders - Drug Targets Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43
Current Neuropharmacology Mitochondria: A Target for Neuroprotective Interventions in Cerebral Ischemia-Reperfusion
Current Pharmaceutical Design Transient Receptor Potential Channels - Emerging Novel Drug Targets for the Treatment of Pain
Current Medicinal Chemistry Bacterial Proteases in Disease – Role in Intracellular Survival, Evasion of Coagulation/ Fibrinolysis Innate Defenses, Toxicoses and Viral Infections
Current Pharmaceutical Design Stem Cell Transplantation: A Promising Therapy for Spinal Cord Injury
Current Stem Cell Research & Therapy The Gastrin-Releasing Peptide Receptor (GRPR) in the Spinal Cord as a Novel Pharmacological Target
Current Neuropharmacology New Perspectives on the Structure and Function of the Na+ Channel Multigene Family
Current Medicinal Chemistry - Central Nervous System Agents Human Embryonic Stem Cell Therapies for Neurodegenerative Diseases
CNS & Neurological Disorders - Drug Targets