Spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and spinal-bulbar muscular atrophy (SBMA) are devastating diseases characterized by the degeneration of motor neurons. Although the molecular causes underlying these diseases differ, recent findings have highlighted the contribution of intrinsic skeletal muscle defects in motor neuron diseases. The use of cell culture and animal models has led to the important finding that muscle defects occur prior to and independently of motor neuron degeneration in motor neuron diseases. In SMA for instance, the muscle specific requirements of the SMA disease-causing gene have been demonstrated by a series of genetic rescue experiments in SMA models. Conditional ALS mouse models expressing a muscle specific mutant SOD1 gene develop atrophy and muscle degeneration in the absence of motor neuron pathology. Treating SBMA mice by over-expressing IGF-1 in a skeletal muscle-specific manner attenuates disease severity and improves motor neuron pathology. In the present review, we provide an in depth description of muscle intrinsic defects, and discuss how they impact muscle function in these diseases. Furthermore, we discuss muscle-specific therapeutic strategies used to treat animal models of SMA, ALS, and SBMA. The study of intrinsic skeletal muscle defects is crucial for the understanding of the pathophysiology of these diseases and will open new therapeutic options for the treatment of motor neuron diseases.
More than a bystander: the contributions of intrinsic skeletal muscle defects in motor neuron diseases
Justin G. Boyer,A. Ferrier,R. Kothary
Published 2013 in Frontiers in Physiology
ABSTRACT
PUBLICATION RECORD
- Publication year
2013
- Venue
Frontiers in Physiology
- Publication date
2013-11-13
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- amyotrophic lateral sclerosis
A motor neuron disease discussed here using conditional mouse models with muscle-targeted mutant SOD1 expression.
Aliases: ALS
- genetic rescue experiments
Experiments that restore gene function in selected tissues to test tissue-specific requirements.
Aliases: rescue experiments
- igf-1
Insulin-like growth factor 1, used here as a skeletal muscle-directed therapeutic factor.
Aliases: insulin-like growth factor 1
- intrinsic skeletal muscle defects
Defects that arise within skeletal muscle itself rather than being secondary to motor neuron loss.
Aliases: muscle intrinsic defects, muscle defects
- motor neuron diseases
A group of disorders characterized by degeneration of motor neurons and associated muscle weakness.
Aliases: MNDs
- muscle-specific mutant sod1 gene
A mutant SOD1 transgene expressed specifically in skeletal muscle in conditional ALS mouse models.
Aliases: muscle-specific SOD1, mutant SOD1 in muscle
- muscle-specific therapeutic strategies
Therapeutic approaches that target skeletal muscle rather than motor neurons directly.
Aliases: skeletal muscle-specific therapy
- spinal-bulbar muscular atrophy
A neuromuscular disease discussed here in the context of skeletal muscle-directed IGF-1 therapy.
Aliases: SBMA, Kennedy disease
- spinal muscular atrophy
A motor neuron disease discussed here as a model for examining muscle-specific gene requirements.
Aliases: SMA
REFERENCES
CITED BY
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