ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
Mutant Cu/Zn-superoxide dismutase associated with amyotrophic lateral sclerosis destabilizes vascular endothelial growth factor mRNA and downregulates its expression.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 84 citations in OpenAlex.
- The myokine FGF21 associates with enhanced survival in ALS and mitigates stress-induced cytotoxicity.Aging · 2025Article
- Targets and Gene Therapy of ALS (Part 1).International journal of molecular sciences · 2025Review
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
- VEGF expression disparities in brainstem motor neurons of the SOD1Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- The role of zinc in the premature brain: functions, outcomes and future research perspectives.Frontiers in pediatrics · 2024Review
- Low Molecular Weight Inhibitors Targeting the RNA-Binding Protein HuR.International journal of molecular sciences · 2023Article
- Role of vascular endothelial growth factor as a critical neurotrophic factor for the survival and physiology of motoneurons.Neural regeneration research · 2023Review
- Evidence and Metabolic Implications for a New Non-Canonical Role of Cu-Zn Superoxide Dismutase.International journal of molecular sciences · 2023Article
- Hu Antigen R (HuR) Protein Structure, Function and Regulation in Hepatobiliary Tumors.Cancers · 2022Review
- Biomarkers in Human Peripheral Blood Mononuclear Cells: The State of the Art in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2022Review
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- RNA Deregulation in Amyotrophic Lateral Sclerosis: The Noncoding Perspective.International journal of molecular sciences · 2021Review
- Neuroprotective Effect of Vascular Endothelial Growth Factor on Motoneurons of the Oculomotor System.International journal of molecular sciences · 2021Review
- Retinal Damage in Amyotrophic Lateral Sclerosis: Underlying Mechanisms.Eye and brain · 2021Review
- Understanding and targeting the disease-related RNA binding protein human antigen R (HuR).Wiley interdisciplinary reviews. RNA · 2020Review
- Widespread FUS mislocalization is a molecular hallmark of amyotrophic lateral sclerosis.Brain : a journal of neurology · 2019Article
- Vascular regression precedes motor neuron loss in the FUS (1-359) ALS mouse model.Disease models & mechanisms · 2019Article
- RNA Dysregulation in Amyotrophic Lateral Sclerosis.Frontiers in genetics · 2018Review
- Unraveling new functions of superoxide dismutase using yeast model system: Beyond its conventional role in superoxide radical scavenging.Journal of microbiology (Seoul, Korea) · 2017Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Vascular endothelial growth factor (VEGF) plays a neuroprotective role in mice harboring mutations of copper-zinc superoxide dismutase 1 (SOD1) in familial amyotrophic lateral sclerosis (ALS). Conversely, the loss of VEGF expression through genetic depletion can give rise to a phenotype resembling ALS independent of SOD1 mutations. Here, we observe a profound downregulation of VEGF mRNA expression in spinal cords of G93A SOD1 mice that occurred early in the course of the disease. Using an in vitro culture model of glial cells expressing mutant SOD1, we demonstrate destabilization and downregulation of VEGF RNA with concomitant loss of protein expression that correlates with level of transgene expression. Using a luciferase reporter assay, we show that this molecular effect is mediated through a portion of the VEGF 3'-untranslated region (UTR) that harbors a class II adenylate/uridylate-rich element. Other mutant forms of SOD1 produced a similar negative effect on luciferase RNA and protein expression. Mobility shift assay with a VEGF 3'-UTR probe reveals an aberrantly migrating complex that contains mutant SOD1. We further show that the RNA stabilizing protein, HuR (human antigen R), is translocated from nucleus to cytoplasm in mutant SOD1 cells in vitro and mouse motor neurons in vivo. In summary, our data suggest that mutant SOD1 gains a novel function, possibly by altering the ribonucleoprotein complex with the VEGF 3'-UTR. We postulate that the resultant dysregulation of VEGF posttranscriptional processing critically reduces the level of this neuroprotective growth factor and accelerates the neurodegenerative process in ALS.
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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.