Abstract
Spinal muscular atrophy (SMA) is the most common genetically inherited neurodegenerative disease resulting in infant mortality. SMA is caused by genetic deletion or mutation in the survival of motor neuron 1 (SMN1) gene, which results in reduced levels of the survival of motor neuron (SMN) protein. SMN protein deficiency preferentially affects α- motor neurons, leading to their degeneration and subsequent atrophy of limb and trunk muscles, progressing to death in severe forms of the disease. More recent studies have shown that SMN protein depletion is detrimental to the functioning of other tissues including skeletal muscle, heart, autonomic and enteric nervous systems, metabolic/endocrine (e.g. pancreas), lymphatic, bone and reproductive system. In this review, we summarize studies discussing SMN protein’s function in various cell and tissue types and their involvement in the context of SMA disease etiology. Taken together, these studies indicate that SMA is a multi-organ disease, which suggests that truly effective disease intervention may require body-wide correction of SMN protein levels.
Keywords: Gene therapy, motor neuron, neuromuscular disease, spinal muscular atrophy, survival of motor neuron, therapeutics.
Current Molecular Medicine
Title:Spinal Muscular Atrophy: More than a Disease of Motor Neurons?
Volume: 16 Issue: 9
Author(s): L. A. Nash, J. K. Burns, J. Warman Chardon, R. Kothary and R. J. Parks
Affiliation:
Keywords: Gene therapy, motor neuron, neuromuscular disease, spinal muscular atrophy, survival of motor neuron, therapeutics.
Abstract: Spinal muscular atrophy (SMA) is the most common genetically inherited neurodegenerative disease resulting in infant mortality. SMA is caused by genetic deletion or mutation in the survival of motor neuron 1 (SMN1) gene, which results in reduced levels of the survival of motor neuron (SMN) protein. SMN protein deficiency preferentially affects α- motor neurons, leading to their degeneration and subsequent atrophy of limb and trunk muscles, progressing to death in severe forms of the disease. More recent studies have shown that SMN protein depletion is detrimental to the functioning of other tissues including skeletal muscle, heart, autonomic and enteric nervous systems, metabolic/endocrine (e.g. pancreas), lymphatic, bone and reproductive system. In this review, we summarize studies discussing SMN protein’s function in various cell and tissue types and their involvement in the context of SMA disease etiology. Taken together, these studies indicate that SMA is a multi-organ disease, which suggests that truly effective disease intervention may require body-wide correction of SMN protein levels.
Export Options
About this article
Cite this article as:
Nash A. L., Burns K. J., Chardon Warman J., Kothary R. and Parks J. R., Spinal Muscular Atrophy: More than a Disease of Motor Neurons?, Current Molecular Medicine 2016; 16 (9) . https://dx.doi.org/10.2174/1566524016666161128113338
DOI https://dx.doi.org/10.2174/1566524016666161128113338 |
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
-
Targeting the Multifaceted HuR Protein, Benefits and Caveats
Current Drug Targets Polyglutamine Protein Trafficking and Neurodegeneration
Current Genomics Transglutaminases as Possible Therapeutic Targets in Neurodegenerative Diseases
Recent Patents on CNS Drug Discovery (Discontinued) Integrating Qualitative and Quantitative Tools for the Detection and Identification of Lectins in Major Human Diseases
Protein & Peptide Letters Role of Mitochondrial Heat-shock Proteins and Immunophilins in Neuro Degenerative Diseases
Current Drug Targets TRP Channels: New Potential Therapeutic Approaches in CNS Neuropathies
CNS & Neurological Disorders - Drug Targets Alternate Strategies of Hsp90 Modulation for the Treatment of Cancer and Other Diseases
Current Topics in Medicinal Chemistry Valosin Containing Protein Associated Fronto-Temporal Lobar Degeneration:Clinical Presentation, Pathologic Features and Pathogenesis
Current Alzheimer Research RNA Splicing Manipulation: Strategies to Modify Gene Expression for a Variety of Therapeutic Outcomes
Current Gene Therapy Functions of Fukutin, a Gene Responsible for Fukuyama Type Congenital Muscular Dystrophy, in Neuromuscular System and Other Somatic Organs
Central Nervous System Agents in Medicinal Chemistry Intracranial MR Dynamics in Clinically Diagnosed Alzheimers Disease: The Emerging Concept of “Pulse Wave Encephalopathy”
Current Alzheimer Research Combined Transcriptomic and Proteomic Analyses of Cerebral Frontal Lobe Tissue Identified RNA Metabolism Dysregulation as One Potential Pathogenic Mechanism in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
Current Neurovascular Research Recent updates on the dynamic association between oxidative stress and neurodegenerative disorders
CNS & Neurological Disorders - Drug Targets Molecular Pathophysiology of Cavernous Nerve Injury and Identification of Strategies for Nerve Function Recovery After Radical Prostatectomy
Current Drug Targets Histone Acetylation as a Potential Therapeutic Target in Motor Neuron Degenerative Diseases
Current Pharmaceutical Design Myopathic Involvement and Mitochondrial Pathology in Kennedy Disease and in Other Motor Neuron Diseases
Current Molecular Medicine Recent Progress and Related Patents on the Applications of Bone Marrow-Derived Stem/Progenitor Cells in Regenerative Medicine and Cancer Therapies
Recent Patents on Regenerative Medicine Contribution of Glucocorticoids and Glucocorticoid Receptors to the Regulation of Neurodegenerative Processes
CNS & Neurological Disorders - Drug Targets Fish Genomes, Comparative Genomics and Vertebrate Evolution
Current Genomics Emerging RNA-based Drugs: siRNAs, microRNAs and Derivates
Central Nervous System Agents in Medicinal Chemistry