ArticleGenes & development2018
Dysregulation of Mdm2 and Mdm4 alternative splicing underlies motor neuron death in spinal muscular atrophy.
Article in Genes & development, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- A standardized framework resolves ambiguity in motor neuron loss across neurodegenerative diseases.Acta neuropathologica communications · 2026Pooled it
- Targeted knockdown of Smn in muscle stem cells induces non-cell autonomous loss of motor neurons.Brain : a journal of neurology · 2026Article
- Incomplete cerebellar circuit restoration limits functional recovery following SMN therapy in severe spinal muscular atrophy.bioRxiv : the preprint server for biology · 2026Article
- A p53-ΔNp73 signaling axis drives selective motor neuron degeneration in spinal muscular atrophy.bioRxiv : the preprint server for biology · 2026Article
- A standardized framework resolves ambiguity in motor neuron loss across neurodegenerative diseases.bioRxiv : the preprint server for biology · 2026Article
- Cerebellar pathology contributes to neurodevelopmental deficits in spinal muscular atrophy.Brain : a journal of neurology · 2026Article
- Polyserine domains are toxic and exacerbate tau pathology in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Identification of p38 MAPK inhibition as a neuroprotective strategy for combinatorial SMA therapy.EMBO molecular medicine · 2025Article
- Proprioceptive synaptic dysfunction is a key feature in mice and humans with spinal muscular atrophy.Brain : a journal of neurology · 2025Article
- Shared interactions of six neurotropic viruses with 38 human proteins: a computational and literature-based exploration of viral interactions and hijacking of human proteins in neuropsychiatric disorders.Discover mental health · 2025Article
- Catecholaminergic dysfunction drives postural and locomotor deficits in a mouse model of spinal muscular atrophy.Cell reports · 2025Article
- Isogenic patient-derived organoids reveal early neurodevelopmental defects in spinal muscular atrophy initiation.Cell reports. Medicine · 2024Article
- A common cellular response to broad splicing perturbations is characterized by metabolic transcript downregulation driven by the Mdm2-p53 axis.Disease models & mechanisms · 2024Article
- Serotonergic dysfunction impairs locomotor coordination in spinal muscular atrophy.Brain : a journal of neurology · 2023Article
- Deletion of ARGLU1 causes global defects in alternative splicing in vivo and mouse cortical malformations primarily via apoptosis.Cell death & disease · 2023Article
- Tumor suppressor p53 regulates heat shock factor 1 protein degradation in Huntington's disease.Cell reports · 2023Article
- Fast Blue and Cholera Toxin-B Survival Guide for Alpha-Motoneurons Labeling: Less Is Better in Young B6SJL Mice, but More Is Better in Aged C57Bl/J Mice.Bioengineering (Basel, Switzerland) · 2023Article
- SMN post-translational modifications in spinal muscular atrophy.Frontiers in cellular neuroscience · 2023Review
- TGS1 impacts snRNA 3'-end processing, ameliorates survival motor neuron-dependent neurological phenotypes in vivo and prevents neurodegeneration.Nucleic acids research · 2022Article
- SMN controls neuromuscular junction integrity through U7 snRNP.Cell reports · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Ubiquitous deficiency in the survival motor neuron (SMN) protein causes death of motor neurons-a hallmark of the neurodegenerative disease spinal muscular atrophy (SMA)-through poorly understood mechanisms. Here, we show that the function of SMN in the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs) regulates alternative splicing of Mdm2 and Mdm4, two nonredundant repressors of p53. Decreased inclusion of critical Mdm2 and Mdm4 exons is most prominent in SMA motor neurons and correlates with both snRNP reduction and p53 activation in vivo. Importantly, increased skipping of Mdm2 and Mdm4 exons regulated by SMN is necessary and sufficient to synergistically elicit robust p53 activation in wild-type mice. Conversely, restoration of full-length Mdm2 and Mdm4 suppresses p53 induction and motor neuron degeneration in SMA mice. These findings reveal that loss of SMN-dependent regulation of Mdm2 and Mdm4 alternative splicing underlies p53-mediated death of motor neurons in SMA, establishing a causal link between snRNP dysfunction and neurodegeneration.
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Registered trials
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.