Abstract
Spinal muscular atrophy (SMA) is caused by mutations that reduce the level of the survival motor neuron protein (SMN) resulting in death of alpha-motor neurons, yet it is unclear why these cells are preferentially affected by a reduction in this ubiquitously-expressed protein. In mouse models of SMA, one of the earliest events detected is defects at the neuromuscular junction (NMJ). Although NMJs are established at a normal frequency, there are structural as well as functional perturbations and a lack of maturation of the primitive synapse. These early defects are followed by loss of the NMJ, denervation of the muscle and onset of muscle atrophy. In this review, we discuss our current understanding of the contribution of NMJ dysfunction in SMA disease pathogenesis, and also provide an overview of therapies currently under preclinical and clinical development for treatment of SMA.
Keywords: Genetic disease, neuromuscular junction, pathogenesis, spinal muscular atrophy.
Current Molecular Medicine
Title:At the “Junction” of Spinal Muscular Atrophy Pathogenesis: The Role of Neuromuscular Junction Dysfunction in SMA Disease Progression
Volume: 13 Issue: 7
Author(s): B. B. Goulet, R. Kothary and R. J. Parks
Affiliation:
Keywords: Genetic disease, neuromuscular junction, pathogenesis, spinal muscular atrophy.
Abstract: Spinal muscular atrophy (SMA) is caused by mutations that reduce the level of the survival motor neuron protein (SMN) resulting in death of alpha-motor neurons, yet it is unclear why these cells are preferentially affected by a reduction in this ubiquitously-expressed protein. In mouse models of SMA, one of the earliest events detected is defects at the neuromuscular junction (NMJ). Although NMJs are established at a normal frequency, there are structural as well as functional perturbations and a lack of maturation of the primitive synapse. These early defects are followed by loss of the NMJ, denervation of the muscle and onset of muscle atrophy. In this review, we discuss our current understanding of the contribution of NMJ dysfunction in SMA disease pathogenesis, and also provide an overview of therapies currently under preclinical and clinical development for treatment of SMA.
Export Options
About this article
Cite this article as:
Goulet B. B., Kothary R. and Parks J. R., At the “Junction” of Spinal Muscular Atrophy Pathogenesis: The Role of Neuromuscular Junction Dysfunction in SMA Disease Progression, Current Molecular Medicine 2013; 13 (7) . https://dx.doi.org/10.2174/15665240113139990044
DOI https://dx.doi.org/10.2174/15665240113139990044 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
- 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
Related Articles
-
Pharmacotherapy for Obesity
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery TGR5 as a Therapeutic Target for Treating Obesity
Current Topics in Medicinal Chemistry An Evidence-Based Review of the Mechanism of Action, Efficacy, and Safety of Biologic Therapies in the Treatment of Psoriasis and Psoriatic Arthritis
Current Medicinal Chemistry Memory Enhancing Effect of Black Pepper in the AlCl3 Induced Neurotoxicity Mouse Model is Mediated Through Its Active Component Chavicine
Current Pharmaceutical Biotechnology Novel Approaches to the Pharmacotherapy of Obesity
Current Pharmaceutical Design Atherosclerotic Plaque Detection by Multi-detector Computed Tomography
Current Cardiology Reviews Metabolic Syndrome X is a Low-Grade Systemic Inflammatory Condition with its Origins in the Perinatal Period
Current Nutrition & Food Science Synthesis, Characterization and Evaluation of Gemfibrozil-Stilbene Hybrid as Antioxidant Agent
Letters in Drug Design & Discovery Abdominal Aortic Calcification: Clinical Significance, Mechanisms and Therapies
Current Pharmaceutical Design Application of NMR Metabolomics to Search for Human Disease Biomarkers
Combinatorial Chemistry & High Throughput Screening Application of Resveratrol in Diabetes: Rationale, Strategies and Challenges
Current Molecular Medicine Review of Cell and Organ Printing Patents
Recent Patents on Biomedical Engineering (Discontinued) Erythropoiesis Stimulating Agents and Anaemia of End-Stage Renal Disease
Cardiovascular & Hematological Agents in Medicinal Chemistry Potential Therapeutic Targeting of Platelet-Mediated Cellular Interactions in Atherosclerosis and Inflammation
Current Medicinal Chemistry Relaxin Receptors - New Drug Targets for Multiple Disease States
Current Drug Targets Statins and Solid Organ Transplantation
Current Pharmaceutical Design Novel Therapeutic Strategies for Dementia
CNS & Neurological Disorders - Drug Targets Pharmacotherapy of Mixed Dyslipidemia in the Metabolic Syndrome
Current Clinical Pharmacology Drug Targets for Obesity and Depression: From Serotonin to Leptin
Current Drug Targets Selective Serotonin Reuptake Inhibitors for Premature Ejaculation: Review of Erectile and Ejaculatory Side Effects
Current Drug Safety