ReviewAntioxidants & redox signaling2009
A role for copper in the toxicity of zinc-deficient superoxide dismutase to motor neurons in amyotrophic lateral sclerosis.
Review in Antioxidants & redox signaling, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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.
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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.
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Who cites it
33 citing papers in PubMed, 75 citations in OpenAlex.
- The Bright and Dark Sides of Nitric Oxide in Neurodegenerative Diseases.Journal of personalized medicine · 2026Review
- The physiological and pathophysiological roles of copper in the nervous system.The European journal of neuroscience · 2024Review
- Hematological, Inflammatory, Coagulation, and Oxidative/Antioxidant Biomarkers as Predictors for Severity and Mortality in COVID-19: A Prospective Cohort-Study.International journal of general medicine · 2023Article
- Stem Cell Transplantation Therapy and Neurological Disorders: Current Status and Future Perspectives.Biology · 2022Review
- Dietary Plant Polyphenols as the Potential Drugs in Neurodegenerative Diseases: Current Evidence, Advances, and Opportunities.Oxidative medicine and cellular longevity · 2022Review
- Review
- DNA damage accumulates and responses are engaged in human ALS brain and spinal motor neurons and DNA repair is activatable in iPSC-derived motor neurons with SOD1 mutations.Acta neuropathologica communications · 2020Article
- An Allosteric Pathway in Copper, Zinc Superoxide Dismutase Unravels the Molecular Mechanism of the G93A Amyotrophic Lateral Sclerosis-Linked Mutation.The journal of physical chemistry letters · 2019Article
- Impaired Cu-Zn Superoxide Dismutase (SOD1) and Calcineurin (Cn) Interaction in ALS: A Presumed Consequence for TDP-43 and Zinc Aggregation in Tg SOD1Neurochemical research · 2019Article
- Cholesterol secosterol aldehyde adduction and aggregation of Cu,Zn-superoxide dismutase: Potential implications in ALS.Redox biology · 2018Article
- Parsing disease-relevant protein modifications from epiphenomena: perspective on the structural basis of SOD1-mediated ALS.Journal of mass spectrometry : JMS · 2017Article
- A Cystine-Rich Whey Supplement (Immunocal®) Provides Neuroprotection from Diverse Oxidative Stress-Inducing AgentsOxidative medicine and cellular longevity · 2017Article
- The microscopic and ultramicroscopic changes in the skeletal muscles, caused by heavy metal salts.Interventional medicine & applied science · 2016Review
- Copper delivery to the CNS by CuATSM effectively treats motor neuron disease in SOD(G93A) mice co-expressing the Copper-Chaperone-for-SOD.Neurobiology of disease · 2016Article
- Blood levels of trace metals and amyotrophic lateral sclerosis.Neurotoxicology · 2016Article
- Paradoxical Roles of Antioxidant Enzymes: Basic Mechanisms and Health Implications.Physiological reviews · 2016Review
- Metal-deficient SOD1 in amyotrophic lateral sclerosis.Journal of molecular medicine (Berlin, Germany) · 2015Review
- Article
- Oxidation of the tryptophan 32 residue of human superoxide dismutase 1 caused by its bicarbonate-dependent peroxidase activity triggers the non-amyloid aggregation of the enzyme.The Journal of biological chemistry · 2014Article
- Clinical perspective on oxidative stress in sporadic amyotrophic lateral sclerosis.Free radical biology & medicine · 2013Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
In the 16 years since mutations to copper, zinc superoxide dismutase (SOD1) were first linked to familial amyotrophic lateral sclerosis (ALS), a multitude of apparently contradictory results have prevented any general consensus to emerge about the mechanism of toxicity. A decade ago, we showed that the loss of zinc from SOD1 results in the remaining copper in SOD1 to become extremely toxic to motor neurons in culture by a mechanism requiring nitric oxide. The loss of zinc causes SOD1 to become more accessible, more redox reactive, and a better catalyst of tyrosine nitration. Although SOD1 mutant proteins have a modestly reduced affinity for zinc, wild-type SOD1 can be induced to lose zinc by dialysis at slightly acidic pH. Our zinc-deficient hypothesis offers a compelling explanation for how mutant SOD1s have an increased propensity to become selectively toxic to motor neurons and also explains how wild-type SOD1 can be toxic in nonfamilial ALS patients. One critical prediction is that a therapeutic agent directed at zinc-deficient mutant SOD1 could be even more effective in treating sporadic ALS patients. Although transgenic mice experiments have yielded contradictory evidence to the zinc-deficient hypothesis, we will review more recent studies that support a role for copper in ALS. A more careful examination of the role of copper and zinc binding to SOD1 may help counter the growing disillusion in the ALS field about understanding the pathological role of SOD1.
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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.