ArticleFrontiers in aging neuroscience2014
Metal-deficient aggregates and diminished copper found in cells expressing SOD1 mutations that cause ALS.
Article in Frontiers in aging neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 71 citations in OpenAlex.
- Review
- Decreased metallothionein-3 expression in the human spinal cord is a common feature of amyotrophic lateral sclerosis and multiple sclerosis.Scientific reports · 2026Article
- Copper Homeostasis and Cuproptosis in Neurological Disorders.Drug design, development and therapy · 2026Review
- Molecular polymorphism of tau aggregates in Pick's disease.Neurobiology of disease · 2025Article
- Copper, Cuproptosis, and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Metal-Induced Genotoxic Events: Possible Distinction Between Sporadic and Familial ALS.Toxics · 2025Review
- Correlative analysis of metallomic gene expression and metal ion content within the mouse hippocampus.Metallomics : integrated biometal science · 2025Article
- Copper Dyshomeostasis and Diabetic Complications: Chelation Strategies for Management.Mini reviews in medicinal chemistry · 2025Review
- Analysis of Conformational Molecular Changes in Cerebrospinal Fluid Using Fourier Transform Infrared Spectroscopy in Neurodegenerative Diseases.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Amyloid fibril structures and ferroptosis activation induced by ALS-causing SOD1 mutations.Science advances · 2024Article
- Inflammation in Metal-Induced Neurological Disorders and Neurodegenerative Diseases.Biological trace element research · 2024Review
- Mass spectrometry imaging of SOD1 protein-metal complexes in SOD1G93A transgenic mice implicates demetalation with pathology.Nature communications · 2024Article
- Copper toxicity and deficiency: the vicious cycle at the core of protein aggregation in ALS.Frontiers in molecular neuroscience · 2024Review
- Copper homeostasis and the ubiquitin proteasome system.Metallomics : integrated biometal science · 2023Review
- A Review of the Role of Curcumin in Metal Induced Toxicity.Antioxidants (Basel, Switzerland) · 2023Review
- Copper homeostasis and cuproptosis in health and disease.Signal transduction and targeted therapy · 2022Review
- Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion.Nature communications · 2022Article
- Hydrogen Peroxide and Amyotrophic Lateral Sclerosis: From Biochemistry to Pathophysiology.Antioxidants (Basel, Switzerland) · 2021Review
- Curcumin and Nano-Curcumin Mitigate Copper Neurotoxicity by Modulating Oxidative Stress, Inflammation, and Akt/GSK-3β Signaling.Molecules (Basel, Switzerland) · 2021Article
- Highly Sensitive and Selective Spiropyran-Based Sensor for Copper(II) Quantification.ACS omega · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Disruptions in metal ion homeostasis have been described in association with amyotrophic lateral sclerosis (ALS) for a number of years but the precise mechanism of involvement is poorly understood. Metal ions are especially important to familial ALS cases caused by mutations in the metalloenzyme copper-zinc superoxide dismutase (SOD1). To investigate the role of metals in aggregation of mutant SOD1, we have examined the localization of metal ions in a cell culture model of overexpression. Chinese hamster ovary cells (CHO-K1) were transfected to overexpress SOD1 fused to yellow fluorescent protein (YFP) to readily identify the transfected cells and the intracellular aggregates that develop in the cells expressing mutant or wild-type (WT) SOD1. The concentration and distribution of iron, copper, and zinc were determined for four SOD1 mutants (A4V, G37R, H80R, and D125H) as well as a WT SOD1 using X-ray fluorescence microscopy (XFM). Results demonstrated that the SOD1 aggregates were metal-deficient within the cells, which is consistent with recent in vitro studies. In addition, all SOD1 mutants showed significantly decreased copper content compared to the WT SOD1 cells, regardless of the mutant's ability to bind copper. These results suggest that SOD1 overexpression creates an unmet demand on the cell for copper. This is particularly true for the SOD1 mutants where copper delivery may also be impaired. Hence, the SOD1 mutants are less stable than WT SOD1 and if copper is limited, aggregate formation of the metal-deficient, mutant SOD1 protein occurs.
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