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
-
Local Drug Delivery to Inner Ear for Treatment of Hearing Loss
Current Drug Therapy Cannabinoids
Current Drug Targets - CNS & Neurological Disorders Medical Management and Risk Reduction of the Cardiovascular Effects of Underwater Diving
Current Vascular Pharmacology Does Cyclic Dependent Kinase 5 Play a Significant Role in Determination of Stroke Outcome? Possible Therapeutic Implications
Central Nervous System Agents in Medicinal Chemistry Potential of Photobiomodulation to Induce Differentiation of Adipose- Derived Mesenchymal Stem Cells into Neural Cells
Current Stem Cell Research & Therapy Promotion of Remyelination by Immunoglobulins: Implications for the Treatment of Multiple Sclerosis
Current Pharmaceutical Design Cholinergic System Dysfunction and Neurodegenerative Diseases: Cause or Effect?
CNS & Neurological Disorders - Drug Targets A Review of Current Animal Models of Osteoarthritis Pain
Current Pharmaceutical Biotechnology Human Tooth Germ Stem Cells Preserve Neuro-Protective Effects after Long-Term Cryo-Preservation
Current Neurovascular Research Anesthesia Issues in Central Nervous System Disorders
Current Aging Science Neuropeptides and Other Chemical Mediators, and the Role of Anti-inflammatory Drugs in Primary Headaches
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Roles and Therapeutic Potential of Metallothioneins in Neurodegenerative Diseases
Current Pharmaceutical Biotechnology Role of Fractalkine (CX3CL1) in Regulating Neuron-Microglia Interactions: Development of Viral-Based CX3CR1 Antagonists
Current Alzheimer Research NMDA Receptors in Glial Cells: Pending Questions
Current Neuropharmacology L-Acetylcarnitine: A Proposed Therapeutic Agent for Painful Peripheral Neuropathies
Current Neuropharmacology Expression and Regulation of Excitation-Contraction Coupling Proteins in Aging Skeletal Muscle
Current Aging Science Angiogenesis-regulating microRNAs and Ischemic Stroke
Current Vascular Pharmacology Modulation of Endoplasmic Reticulum Stress: An Opportunity to Prevent Neurodegeneration?
CNS & Neurological Disorders - Drug Targets The Nitric Oxide Signaling Pathway in the Penis
Current Pharmaceutical Design Stem Cell and Gene Therapeutic Strategies for the Treatment of Multiple Sclerosis
Current Molecular Medicine