ReviewGene therapy2017
Developmental regulation of SMN expression: pathophysiological implications and perspectives for therapy development in spinal muscular atrophy.
Review in Gene therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Maternal-Fetal Administration of Risdiplam Partially Rescues the SMNΔ7 Mouse Model of Spinal Muscular Atrophy.Annals of neurology · 2026Article
- Survival Motor Neuron Protein Requirement-Supply Mismatch in Spinal Muscular Atrophy: A Conceptual Framework.Advances in therapy · 2026Review
- The role of vascular pathology in SMA: implications for pathogenesis and treatment.Frontiers in cellular neuroscience · 2026Review
- Prenatal SMN-dependent defects in translation uncover reversible primary cilia phenotypes in spinal muscular atrophy.JCI insight · 2025Article
- Munc13-1 restoration mitigates presynaptic pathology in spinal muscular atrophy.Nature communications · 2025Article
- Loss of synaptic Munc13-1 underlies neurotransmission abnormalities in spinal muscular atrophy.Cellular and molecular life sciences : CMLS · 2025Article
- Preemptive dual therapy for children at risk for infantile-onset spinal muscular atrophy.Annals of clinical and translational neurology · 2024Article
- What could be the function of the spinal muscular atrophy-causing protein SMN in macrophages?Frontiers in immunology · 2024Review
- NSC Physiological Features in Spinal Muscular Atrophy: SMN Deficiency Effects on Neurogenesis.International journal of molecular sciences · 2022Review
- SMN Is Physiologically Downregulated at Wild-Type Motor Nerve Terminals but Aggregates Together with Neurofilaments in SMA Mouse Models.Biomolecules · 2022Article
- Therapy development for spinal muscular atrophy: perspectives for muscular dystrophies and neurodegenerative disorders.Neurological research and practice · 2022Review
- In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy.Brain sciences · 2021Review
- Modulating the endoplasmic reticulum stress response attenuates neurodegeneration in aDisease models & mechanisms · 2020Article
- Temperature-sensitive spinal muscular atrophy-causing point mutations lead to SMN instability, locomotor defects and premature lethality inDisease models & mechanisms · 2020Article
- R-Roscovitine Improves Motoneuron Function in Mouse Models for Spinal Muscular Atrophy.iScience · 2020Article
- Muscleblind acts as a modifier of FUS toxicity by modulating stress granule dynamics and SMN localization.Nature communications · 2019Article
- The Role of RNA Binding Proteins for Local mRNA Translation: Implications in Neurological Disorders.Frontiers in molecular biosciences · 2019Review
- The role of survival motor neuron protein (SMN) in protein homeostasis.Cellular and molecular life sciences : CMLS · 2018Review
- Treating pediatric neuromuscular disorders: The future is now.American journal of medical genetics. Part A · 2018Review
- The state of gene therapy research in Africa, its significance and implications for the future.Gene therapy · 2017Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal muscular atrophy (SMA), the predominant form of motoneuron disease in children and young adults is caused by loss of function of the SMN protein. On the basis of a disrupted splice acceptor site in exon 7, transcripts from a second SMN gene in humans called SMN2 cannot give rise to SMN protein at sufficient levels for maintaining function of motoneurons and motor circuits. First clinical trials with Spinraza/Nusinersen, a drug that counteracts disrupted splicing of SMN2 transcripts, have shown that elevating SMN levels can successfully interfere with motoneuron dysfunction. This review summarizes current knowledge about the pathophysiological alterations in Smn-deficient motoneurons, which lead to defective neuromuscular transmission and altered spinal circuit formation. Both pathological mechanisms are important targets for therapeutic intervention. However, the developmental time window when therapeutic interventions ideally should start is not known. Endogenous SMN expression both from SMN1 and SMN2 genes is high at early developmental stages and declines progressively in humans and mice. Thus, therapeutic SMN upregulation should start just before SMN declines below a critical threshold, and before irreversible defects occur at neuromuscular junctions and in spinal circuits. Previous results indicate that loss of Smn function leads to synaptic dysfunction during a stage of neuromuscular development when synaptic strength determines which synapses are maintained or not. This time window appears as an important target for therapy, which possibly could be supported by additional strategies that strengthen synaptic transmission.
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