ArticleThe Journal of clinical investigation2014
Dysregulation of ubiquitin homeostasis and β-catenin signaling promote spinal muscular atrophy.
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 114 papers, 2 of them syntheses that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
114 citing papers in PubMed, 2 syntheses or guidelines pooled it, 175 citations in OpenAlex.
- Drug treatment for spinal muscular atrophy types II and III.The Cochrane database of systematic reviews · 2020Pooled it
- Drug treatment for spinal muscular atrophy type I.The Cochrane database of systematic reviews · 2019Pooled it
- A Comparative Study of SMN Protein and mRNA in Blood and Fibroblasts in Patients with Spinal Muscular Atrophy and Healthy Controls.PloS one · 2016Trial
- The ubiquitin system in heart and vessel pathobiology: From mechanisms to therapeutic strategies.Genes & diseases · 2026Review
- Transcriptional reprogramming in SMA mouse hearts reveals signatures of early heart failure and dysregulated calcium signaling.Human molecular genetics · 2025Article
- Treating neuromuscular diseases: unveiling gene therapy breakthroughs and pioneering future applications.Journal of biomedical science · 2025Review
- UtilizingJournal of developmental biology · 2025Review
- Patient-specific responses toMolecular therapy. Methods & clinical development · 2024Article
- Review
- Clinical and Genetic Profiles of 5q- and Non-5q-Spinal Muscular Atrophy Diseases in Pediatric Patients.Genes · 2024Review
- Isogenic patient-derived organoids reveal early neurodevelopmental defects in spinal muscular atrophy initiation.Cell reports. Medicine · 2024Article
- Ubiquitination Insight from Spinal Muscular Atrophy-From Pathogenesis to Therapy: A Muscle Perspective.International journal of molecular sciences · 2024Review
- Altered mitochondrial function in fibroblast cell lines derived from disease carriers of spinal muscular atrophy.Communications medicine · 2024Article
- The SMN-ribosome interplay: a new opportunity for Spinal Muscular Atrophy therapies.Biochemical Society transactions · 2024Review
- Modeling Spinal Muscular Atrophy in Zebrafish: Current Advances and Future Perspectives.International journal of molecular sciences · 2024Review
- Diving deep: zebrafish models in motor neuron degeneration research.Frontiers in neuroscience · 2024Review
- Innovating spinal muscular atrophy models in the therapeutic era.Disease models & mechanisms · 2023Article
- WNT-β Catenin Signaling as a Potential Therapeutic Target for Neurodegenerative Diseases: Current Status and Future Perspective.Diseases (Basel, Switzerland) · 2023Review
- Sex Difference in Spinal Muscular Atrophy Patients - are Males More Vulnerable?Journal of neuromuscular diseases · 2023Article
- An Optimized Comparative Proteomic Approach as a Tool in Neurodegenerative Disease Research.Cells · 2022Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 7 institutions in 2 countries.
Funding
Abstract
The autosomal recessive neurodegenerative disease spinal muscular atrophy (SMA) results from low levels of survival motor neuron (SMN) protein; however, it is unclear how reduced SMN promotes SMA development. Here, we determined that ubiquitin-dependent pathways regulate neuromuscular pathology in SMA. Using mouse models of SMA, we observed widespread perturbations in ubiquitin homeostasis, including reduced levels of ubiquitin-like modifier activating enzyme 1 (UBA1). SMN physically interacted with UBA1 in neurons, and disruption of Uba1 mRNA splicing was observed in the spinal cords of SMA mice exhibiting disease symptoms. Pharmacological or genetic suppression of UBA1 was sufficient to recapitulate an SMA-like neuromuscular pathology in zebrafish, suggesting that UBA1 directly contributes to disease pathogenesis. Dysregulation of UBA1 and subsequent ubiquitination pathways led to β-catenin accumulation, and pharmacological inhibition of β-catenin robustly ameliorated neuromuscular pathology in zebrafish, Drosophila, and mouse models of SMA. UBA1-associated disruption of β-catenin was restricted to the neuromuscular system in SMA mice; therefore, pharmacological inhibition of β-catenin in these animals failed to prevent systemic pathology in peripheral tissues and organs, indicating fundamental molecular differences between neuromuscular and systemic SMA pathology. Our data indicate that SMA-associated reduction of UBA1 contributes to neuromuscular pathogenesis through disruption of ubiquitin homeostasis and subsequent β-catenin signaling, highlighting ubiquitin homeostasis and β-catenin as potential therapeutic targets for SMA.
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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.