ArticleThe Journal of biological chemistry2013
Calcium ions promote superoxide dismutase 1 (SOD1) aggregation into non-fibrillar amyloid: a link to toxic effects of calcium overload in amyotrophic lateral sclerosis (ALS)?
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 56 citations in OpenAlex.
- Nanoscale Analysis beyond Imaging by Atomic Force Microscopy: Molecular Perspectives on Oncology and Neurodegeneration.Small science · 2025Review
- Pharmacological activation of BK channels protects against LPS-induced pneumonia.Scientific reports · 2025Article
- Heavy Metal Mediated Progressive Degeneration and Its Noxious Effects on Brain Microenvironment.Biological trace element research · 2024Review
- Serum antioxidant enzymes in spinal stenosis patients with lumbar disc herniation: correlation with degeneration severity and spinal fusion rate.BMC musculoskeletal disorders · 2023Article
- Targeting the Mitochondrial Protein VDAC1 as a Potential Therapeutic Strategy in ALS.International journal of molecular sciences · 2022Article
- SOD1 in ALS: Taking Stock in Pathogenic Mechanisms and the Role of Glial and Muscle Cells.Antioxidants (Basel, Switzerland) · 2022Review
- Delineating the Aggregation-Prone Hotspot Regions (Peptides) in the Human Cu/Zn Superoxide Dismutase 1.ACS omega · 2021Article
- Ryanodine Receptors: A Potential Treatment Target in Various Neurodegenerative Disease.Cellular and molecular neurobiology · 2021Review
- Review
- Evaluation of Peptide/Protein Self-Assembly and Aggregation by Spectroscopic Methods.Molecules (Basel, Switzerland) · 2020Review
- Verapamil Ameliorates Motor Neuron Degeneration and Improves Lifespan in the SOD1Aging and disease · 2019Article
- Calcium Dyshomeostasis and Lysosomal CaCells · 2019Review
- Carcinogenesis and Reactive Oxygen Species Signaling: Interaction of the NADPH Oxidase NOX1-5 and Superoxide Dismutase 1-3 Signal Transduction Pathways.Antioxidants & redox signaling · 2019Review
- Determining the Effect of Catechins on SOD1 Conformation and Aggregation by Ion Mobility Mass Spectrometry Combined with Optical Spectroscopy.Journal of the American Society for Mass Spectrometry · 2018Article
- MIF inhibits the formation and toxicity of misfolded SOD1 amyloid aggregates: implications for familial ALS.Cell death & disease · 2018Article
- Disulfide cross-linked multimers of TDP-43 and spinal motoneuron loss in a TDP-43Scientific reports · 2017Article
- A computational combinatorial approach identifies a protein inhibitor of superoxide dismutase 1 misfolding, aggregation, and cytotoxicity.The Journal of biological chemistry · 2017Article
- Essential trace elements in amyotrophic lateral sclerosis (ALS): Results in a population of a risk area of Italy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2017Article
- The Role of Metal Binding in the Amyotrophic Lateral Sclerosis-Related Aggregation of Copper-Zinc Superoxide Dismutase.Molecules (Basel, Switzerland) · 2017Review
- Zinc Binding to S100B Affords Regulation of Trace Metal Homeostasis and Excitotoxicity in the Brain.Frontiers in molecular neuroscience · 2017Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Imbalance in metal ion homeostasis is a hallmark in neurodegenerative conditions involving protein deposition, and amyotrophic lateral sclerosis (ALS) is no exception. In particular, Ca(2+) dysregulation has been shown to correlate with superoxide dismutase-1 (SOD1) aggregation in a cellular model of ALS. Here we present evidence that SOD1 aggregation is enhanced and modulated by Ca(2+). We show that at physiological pH, Ca(2+) induces conformational changes that increase SOD1 β-sheet content, as probed by far UV CD and attenuated total reflectance-FTIR, and enhances SOD1 hydrophobicity, as probed by ANS fluorescence emission. Moreover, dynamic light scattering analysis showed that Ca(2+) boosts the onset of SOD1 aggregation. In agreement, Ca(2+) decreases SOD1 critical concentration and nucleation time during aggregation kinetics, as evidenced by thioflavin T fluorescence emission. Attenuated total reflectance FTIR analysis showed that Ca(2+) induced aggregates consisting preferentially of antiparallel β-sheets, thus suggesting a modulation effect on the aggregation pathway. Transmission electron microscopy and analysis with conformational anti-fibril and anti-oligomer antibodies showed that oligomers and amyloidogenic aggregates constitute the prevalent morphology of Ca(2+)-induced aggregates, thus indicating that Ca(2+) diverts SOD1 aggregation from fibrils toward amorphous aggregates. Interestingly, the same heterogeneity of conformations is found in ALS-derived protein inclusions. We thus hypothesize that transient variations and dysregulation of cellular Ca(2+) levels contribute to the formation of SOD1 aggregates in ALS patients. In this scenario, Ca(2+) may be considered as a pathogenic effector in the formation of ALS proteinaceous inclusions.
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