ArticleHuman molecular genetics2012
Mutant superoxide dismutase 1 (SOD1), a cause of amyotrophic lateral sclerosis, disrupts the recruitment of SMN, the spinal muscular atrophy protein to nuclear Cajal bodies.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- A variant of the Hspa8 synaptic chaperone modifies disease in a SOD1Experimental neurology · 2025Article
- An Optimized Comparative Proteomic Approach as a Tool in Neurodegenerative Disease Research.Cells · 2022Review
- Article
- Genetic modifiers ameliorate endocytic and neuromuscular defects in a model of spinal muscular atrophy.BMC biology · 2020Article
- VRK1 (Y213H) homozygous mutant impairs Cajal bodies in a hereditary case of distal motor neuropathy.Annals of clinical and translational neurology · 2020Article
- The Small-Molecule Flunarizine in Spinal Muscular Atrophy Patient Fibroblasts Impacts on the Gemin Components of the SMN Complex and TDP43, an RNA-Binding Protein Relevant to Motor Neuron Diseases.Frontiers in molecular biosciences · 2020Article
- SMN complex member Gemin3 self-interacts and has a functional relationship with ALS-linked proteins TDP-43, FUS and Sod1.Scientific reports · 2019Article
- Disruption of RNA Metabolism in Neurological Diseases and Emerging Therapeutic Interventions.Neuron · 2019Review
- CBP-mediated SMN acetylation modulates Cajal body biogenesis and the cytoplasmic targeting of SMN.Cellular and molecular life sciences : CMLS · 2018Article
- Cajal bodies in neurons.RNA biology · 2017Review
- Functional interaction between FUS and SMN underlies SMA-like splicing changes in wild-type hFUS mice.Scientific reports · 2017Article
- Diabetic polyneuropathy, sensory neurons, nuclear structure and spliceosome alterations: a role for CWC22.Disease models & mechanisms · 2017Article
- Article
- Motor Neuron Gene Therapy: Lessons from Spinal Muscular Atrophy for Amyotrophic Lateral Sclerosis.Frontiers in molecular neuroscience · 2017Review
- Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS.Scientific reports · 2016Article
- Old versus New Mechanisms in the Pathogenesis of ALS.Brain pathology (Zurich, Switzerland) · 2016Review
- Copy Number Variations in the Survival Motor Neuron Genes: Implications for Spinal Muscular Atrophy and Other Neurodegenerative Diseases.Frontiers in molecular biosciences · 2016Review
- Selective Neuromuscular Denervation in Taiwanese Severe SMA Mouse Can Be Reversed by Morpholino Antisense Oligonucleotides.PloS one · 2016Article
- ALS-causative mutations in FUS/TLS confer gain and loss of function by altered association with SMN and U1-snRNP.Nature communications · 2015Article
- Nuclear localization of SMN and FUS is not altered in fibroblasts from patients with sporadic ALS.Amyotrophic lateral sclerosis & frontotemporal degeneration · 2014Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are among the most common motor neuron diseases to afflict the human population. A deficiency of the survival of motor neuron (SMN) protein causes SMA and is also reported to be an exacerbating factor in the development of ALS. However, pathways linking the two diseases have yet to be defined and it is not clear precisely how the pathology of ALS is aggravated by reduced SMN or whether mutant proteins underlying familial forms of ALS interfere with SMN-related biochemical pathways to exacerbate the neurodegenerative process. In this study, we show that mutant superoxide dismutase-1 (SOD1), a cause of familial ALS, profoundly alters the sub-cellular localization of the SMN protein, preventing the formation of nuclear 'gems' by disrupting the recruitment of the protein to Cajal bodies. Overexpressing the SMN protein in mutant SOD1 mice, a model of familial ALS, alleviates this phenomenon, most likely in a cell-autonomous manner, and significantly mitigates the loss of motor neurons in the spinal cord and in culture dishes. In the mice, the onset of the neuromuscular phenotype is delayed and motor function enhanced, suggestive of a therapeutic benefit for ALS patients treated with agents that augment the SMN protein. Nevertheless, this finding is tempered by an inability to prolong survival, a limitation most likely imposed by the inexorable denervation that characterizes ALS and eventually disrupts the neuromuscular synapses even in the presence of increased SMN.
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