Related Experiment Video
Updated: Oct 21, 2025
Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents
Published on: August 10, 2018
MicroRNA expression in animal models of amyotrophic lateral sclerosis and potential therapeutic approaches
Bridget Martinez1, Philip V Peplow2
1Physical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, USA; Department of Medicine, St. Georges University School of Medicine, Grenada.
Abstract:
A review of recent animal models of amyotrophic lateral sclerosis showed a large number of miRNAs had altered levels of expression in the brain and spinal cord, motor neurons of spinal cord and brainstem, and hypoglossal, facial, and red motor nuclei and were mostly upregulated. Among the miRNAs found to be upregulated in two of the studies were miR-21, miR-155, miR-125b, miR-146a, miR-124, miR-9, and miR-19b, while those downregulated in two of the studies included miR-146a, miR-29, miR-9, and miR-125b. A change of direction in miRNA expression occurred in some tissues when compared (e.g., miR-29b-3p in cerebellum and spinal cord of wobbler mice at 40 days), or at different disease stages (e.g., miR-200a in spinal cord of SOD1(G93A) mice at 95 days vs. 108 and 112 days). In the animal models, suppression of miR-129-5p resulted in increased lifespan, improved muscle strength, reduced neuromuscular junction degeneration, and tended to improve motor neuron survival in the SOD1(G93A) mouse model. Suppression of miR-155 was also associated with increased lifespan, while lowering of miR-29a tended to improve lifespan in males and increase muscle strength in SOD1(G93A) mice. Overexpression of members of miR-17~92 cluster improved motor neuron survival in SOD1(G93A) mice. Treatment with an artificial miRNA designed to target hSOD1 increased lifespan and improved muscle strength in SOD1(G93A) animals. Further studies with animal models of amyotrophic lateral sclerosis are warranted to validate these findings and identify specific miRNAs whose suppression or directed against hSOD1 results in increased lifespan, improved muscle strength, reduced neuromuscular junction degeneration, and improved motor neuron survival in SOD1(G93A) animals.
Insights
MicroRNAs (miRNAs) show altered expression in animal models of amyotrophic lateral sclerosis (ALS). Targeting specific miRNAs can improve motor neuron survival and extend lifespan in ALS mouse models.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression.
- Altered miRNA expression is implicated in the pathogenesis of ALS.
Purpose of the Study:
- To review altered miRNA expression in animal models of ALS.
- To investigate the therapeutic potential of targeting miRNAs in ALS.
Main Methods:
- Review of recent literature on miRNA expression in ALS animal models.
- Analysis of miRNA expression patterns in various tissues and disease stages.
- Evaluation of the effects of miRNA manipulation on ALS phenotypes in animal models.
Main Results:
- A significant number of miRNAs exhibit altered expression in the central nervous system of ALS animal models.
- Specific miRNAs, such as miR-129-5p, miR-155, and miR-29a, when suppressed or modulated, demonstrated beneficial effects on lifespan, muscle strength, and motor neuron survival.
- Overexpression of the miR-17~92 cluster and targeting hSOD1 with artificial miRNAs also showed therapeutic promise.
Conclusions:
- miRNAs represent potential therapeutic targets for ALS.
- Further research in animal models is crucial to validate these findings and develop miRNA-based therapies for ALS.
