ArticleThe Journal of clinical investigation2014
Requirement of enhanced Survival Motoneuron protein imposed during neuromuscular junction maturation.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
84 citing papers in PubMed.
- Age-dependent SMN expression in disease-relevant tissue and implications for SMA treatment.The Journal of clinical investigation · 2019Trial
- Survival Motor Neuron Protein Requirement-Supply Mismatch in Spinal Muscular Atrophy: A Conceptual Framework.Advances in therapy · 2026Review
- Aging-Related Changes in the Injury Response of the Peripheral Nervous System.Neuroscience bulletin · 2026Review
- Neurodegenerative spliceosomopathies.Frontiers in cell and developmental biology · 2026Review
- Conditional knockout mouse model demonstrates that Copa expression is required for viability in development and adulthood.Biochemical and biophysical research communications · 2025Article
- In Search of Spinal Muscular Atrophy Disease Modifiers.International journal of molecular sciences · 2024Review
- Improved therapeutic approach for spinal muscular atrophy via ubiquitination-resistant survival motor neuron variant.Journal of cachexia, sarcopenia and muscle · 2024Article
- Beyond Motor Neurons in Spinal Muscular Atrophy: A Focus on Neuromuscular Junction.International journal of molecular sciences · 2024Review
- Chaperoning the chaperones: Proteomic analysis of the SMN complex reveals conserved and etiologic connections to the proteostasis network.bioRxiv : the preprint server for biology · 2024Article
- Article
- Proteomic analysis of the SMN complex reveals conserved and etiologic connections to the proteostasis network.Frontiers in RNA research · 2024Article
- Fatigue in Spinal Muscular Atrophy: a fundamental open issue.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2024Review
- Innovating spinal muscular atrophy models in the therapeutic era.Disease models & mechanisms · 2023Article
- A spinal muscular atrophy modifier implicates the SMN protein in SNARE complex assembly at neuromuscular synapses.Neuron · 2023Article
- Base editing rescue of spinal muscular atrophy in cells and in mice.Science (New York, N.Y.) · 2023Article
- Generation of functional posterior spinal motor neurons from hPSCs-derived human spinal cord neural progenitor cells.Cell regeneration (London, England) · 2023Article
- Long-TermInternational journal of molecular sciences · 2023Article
- SMN Is Physiologically Downregulated at Wild-Type Motor Nerve Terminals but Aggregates Together with Neurofilaments in SMA Mouse Models.Biomolecules · 2022Article
- Article
- Dysregulation of Tweak and Fn14 in skeletal muscle of spinal muscular atrophy mice.Skeletal muscle · 2022Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
Spinal muscular atrophy is a common motor neuron disease caused by low survival motoneuron (SMN), a key protein in the proper splicing of genes. Restoring the protein is therefore a promising therapeutic strategy. Implementation of this strategy, however, depends on defining the temporal requirements for SMN. Here, we used controlled knockdown of SMN in transgenic mice to determine the precise postnatal stage requirements for this protein. Reducing SMN in neonatal mice resulted in a classic SMA-like phenotype. Unexpectedly, depletion of SMN in adults had relatively little effect. Insensitivity to low SMN emerged abruptly at postnatal day 17, which coincided with establishment of the fully mature neuromuscular junction (NMJ). Mature animals depleted of SMN eventually exhibited evidence of selective neuromuscular pathology that was made worse by traumatic injury. The ability to regenerate the mature NMJ in aged or injured SMN-depleted mice was grossly impaired, a likely consequence of the inability to meet the surge in demand for motoneuronal SMN that was seen in controls. Our results demonstrate that relative maturity of the NMJ determines the temporal requirement for the SMN protein. These observations suggest that the use of potent but potentially deleterious SMN-enhancing agents could be tapered in human patients once the neuromuscular system matures and reintroduced as needed to enhance SMN for remodeling aged or injured NMJs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.