Abstract
Myasthenia gravis is a muscle weakness disease characterized by autoantibodies that target components of the neuromuscular junction, impairing synaptic transmission. The most common form of myasthenia gravis involves antibodies that bind the nicotinic acetylcholine receptors in the postsynaptic membrane. Many of the remaining cases are due to antibodies against muscle specific tyrosine kinase (MuSK). Recently, autoantibodies against LRP4 (another component of the MuSK signaling complex in the postsynaptic membrane) were identified as the likely cause of myasthenia gravis in some patients. Fatiguing weakness is the common symptom in all forms of myasthenia gravis, but muscles of the body are differentially affected, for reasons that are not fully understood. Much of what we have learnt about the immunological and neurobiological aspects of the pathogenesis derives from mouse models. The most widely used mouse models involve either passive transfer of autoantibodies, or active immunization of the mouse with acetylcholine receptors or MuSK protein. These models can provide a robust replication of many of the features of the human disease. Depending upon the protocol, acute fatiguing weakness develops 2 - 14 days after the start of autoantibody injections (passive transfer) or might require repeated immunizations over several weeks (active models). Here we review mouse models of myasthenia gravis, including what they have contributed to current understanding of the pathogenic mechanisms and their current application to the testing of therapeutics.
Keywords: Autoantibodies, nicotinic receptors, antigenic modulation, membrane attack complex, muscle specific kinase, myasthenia gravis, fatigue.
Current Pharmaceutical Design
Title:Mouse Models of Myasthenia Gravis
Volume: 21 Issue: 18
Author(s): Joanne Ban and William D. Phillips
Affiliation:
Keywords: Autoantibodies, nicotinic receptors, antigenic modulation, membrane attack complex, muscle specific kinase, myasthenia gravis, fatigue.
Abstract: Myasthenia gravis is a muscle weakness disease characterized by autoantibodies that target components of the neuromuscular junction, impairing synaptic transmission. The most common form of myasthenia gravis involves antibodies that bind the nicotinic acetylcholine receptors in the postsynaptic membrane. Many of the remaining cases are due to antibodies against muscle specific tyrosine kinase (MuSK). Recently, autoantibodies against LRP4 (another component of the MuSK signaling complex in the postsynaptic membrane) were identified as the likely cause of myasthenia gravis in some patients. Fatiguing weakness is the common symptom in all forms of myasthenia gravis, but muscles of the body are differentially affected, for reasons that are not fully understood. Much of what we have learnt about the immunological and neurobiological aspects of the pathogenesis derives from mouse models. The most widely used mouse models involve either passive transfer of autoantibodies, or active immunization of the mouse with acetylcholine receptors or MuSK protein. These models can provide a robust replication of many of the features of the human disease. Depending upon the protocol, acute fatiguing weakness develops 2 - 14 days after the start of autoantibody injections (passive transfer) or might require repeated immunizations over several weeks (active models). Here we review mouse models of myasthenia gravis, including what they have contributed to current understanding of the pathogenic mechanisms and their current application to the testing of therapeutics.
Export Options
About this article
Cite this article as:
Ban Joanne and Phillips D. William, Mouse Models of Myasthenia Gravis, Current Pharmaceutical Design 2015; 21 (18) . https://dx.doi.org/10.2174/1381612821666150316123233
DOI https://dx.doi.org/10.2174/1381612821666150316123233 |
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
-
Dendritic Cell Immunotherapy for Malignant Gliomas
Reviews on Recent Clinical Trials ADP-Ribosyltransferases and Poly ADP-Ribosylation
Current Protein & Peptide Science Regulation of Granulocyte Apoptosis by Hemopoietic Growth Factors, Cytokines and Drugs: Potential Relevance to Allergic Inflammation
Current Drug Targets - Inflammation & Allergy Novel Imaging Techniques in Acute Kidney Injury
Current Drug Targets Expression of Defensins in Gingiva and Their Role in Periodontal Health and Disease
Current Pharmaceutical Design Phenotypic Alteration of Bone Marrow HSC and Microenvironmental Association in Experimentally Induced Leukemia
Current Stem Cell Research & Therapy The Pharmacological Treatment of Cachexia
Current Drug Targets EphA2-Dependent Molecular Targeting Therapy for Malignant Tumors
Current Cancer Drug Targets Long-circulating Targeted Nanoparticles for Cancer Therapy
Current Nanoscience Cell Death Mechanisms in Stroke and Novel Molecular and Cellular Treatment Options
Current Neuropharmacology Direct Targeting of the Ras GTPase Superfamily Through Structure- Based Design
Current Topics in Medicinal Chemistry Immunogenicity and Tumorigenicity of Pluripotent Stem Cells and their Derivatives: Genetic and Epigenetic Perspectives
Current Stem Cell Research & Therapy MicroRNAs in Cancer: Small Molecules, Big Chances
Anti-Cancer Agents in Medicinal Chemistry Cancer/Testis Antigens Trigger Epithelial-Mesenchymal Transition and Genesis of Cancer Stem-Like Cells
Current Pharmaceutical Design <i>In Vitro</i> Anti-proliferative Properties of Flavonoids Isolated from <i>Artocarpus Heterophyllus</i> on Cancer Cell Lines
The Natural Products Journal The Development of MetAP-2 Inhibitors in Cancer Treatment
Current Medicinal Chemistry Kinetics of Vascular Targeted Monoclonal Antibody
Current Drug Delivery Genetically Modified Cellular Vaccines for Therapy of Human Papilloma Virus Type 16 (HPV 16)-Associated Tumours
Current Cancer Drug Targets Younger for Longer: Insulin Signalling, Immunity and Ageing
Current Aging Science Advances in Transient Receptor Potential Vanilloid-2 Channel Expression and Function in Tumor Growth and Progression
Current Protein & Peptide Science