Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase
Abstract
Mutations in copper, zinc superoxide dismutase (SOD) have been implicated in the selective death of motor neurons in 2 percent of amyotrophic lateral sclerosis (ALS) patients. The loss of zinc from either wild-type or ALS-mutant SODs was sufficient to induce apoptosis in cultured motor neurons. Toxicity required that copper be bound to SOD and depended on endogenous production of nitric oxide. When replete with zinc, neither ALS-mutant nor wild-type copper, zinc SODs were toxic, and both protected motor neurons from trophic factor withdrawal. Thus, zinc-deficient SOD may participate in both sporadic and familial ALS by an oxidative mechanism involving nitric oxide.
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Prior reports suggest swelling-evoked taurine release in the brain, including astrocytes and neurons.
“Prior reports suggest swelling-evoked taurine release in the brain, including astrocytes and neurons.74,75”
From Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages (2026) · cites this paper as [74]
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Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages
Guan, C., Ryu, S., Dong, M., Zhu, Y., Maeda, R., Youm, Y.-H., Mohanty, S., Kim, H.-H., Orliaguet, L., Dlugos, T., et al. (2026) · Cell · doi:10.1016/j.cell.2026.09.061
- Authors
- Estévez, A. G., Crow, J. P., Sampson, J. B., Reiter, C., Zhuang, Y., Richardson, G. J., Tarpey, M. M., Barbeito, L., & Beckman, J. S.
- Affiliations
- Departments of Anesthesiology,
- University of Alabama at Birmingham (US)
- Universidad de la República de Uruguay (UY)
- Corresponding author
- Crow, John P.
- Beckman, Joseph S.
- Venue
- Science
- Published
- 1999-12-24
- Volume
- 286
- Issue
- 5449
- Pages
- 2498-2500
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1988849173
- Cited by
- 596
- References
- 3
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 8 · 2023: 3 · 2022: 7 · 2021: 10 · 2020: 11 · 2019: 4 · 2018: 4 · 2017: 8 · 2016: 9 · 2015: 11 · 2014: 16 · 2013: 22 · 2012: 33
- FWCI
- 37.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (7r01hl058209-05)
- National Heart, Lung, and Blood Institute (R01 HL 58209)
- National Institute of Neurological Disorders and Stroke (R01 NS33291, R01 NS36761, R01NS033291, R01NS036761)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- amyotrophic lateral sclerosis, copper-zinc superoxide dismutase, zinc deficiency, nitric oxide, apoptosis, motor neurons, copper binding, oxidative stress, trophic factor withdrawal, familial ALS
- MeSH terms
- Amyotrophic Lateral Sclerosis, Animals, Cells, Cultured, Chelating Agents, Copper, Fluoresceins, Liposomes, Motor Neurons, Mutation, Nitrates, Nitric Oxide, Oxidation-Reduction, Superoxides, Superoxide Dismutase, Zinc, Apoptosis, Nitric Oxide Synthase, Brain-Derived Neurotrophic Factor, Rats, Nitric Oxide Synthase Type I
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