A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase

@article{Melov1998ANN,
  title={A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase},
  author={Simon Melov and Julie A. Schneider and Brian J. Day and Douglas A. Hinerfeld and Pinar E. Coskun and Suzanne S. Mirra and James D. Crapo and Douglas C. Wallace},
  journal={Nature Genetics},
  year={1998},
  volume={18},
  pages={159-163}
}
Reactive oxygen species (ROS) have been implicated in a wide range of degenerative processes including amyotrophic lateral sclerosis, ischemic heart disease, Alzheimer disease, Parkinson disease and aging1–5. ROS are generated by mitochondria as the toxic by-products of oxidative phosphorylation, their energy generating pathway6,7. Genetic inactivation of the mitochondrial form of superoxide dismutase in mice results in dilated cardiomyopathy, hepatic lipid accumulation and early neonatal… Expand
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References

SHOWING 1-10 OF 24 REFERENCES
Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice.
  • R. Lebovitz, H. Zhang, +5 authors M. Matzuk
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1996
TLDR
Observations indicate that SOD2 deficiency causes increased susceptibility to oxidative mitochondrial injury in central nervous system neurons, cardiac myocytes, and other metabolically active tissues after postnatal exposure to ambient oxygen concentrations. Expand
An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria
Mutations in Cu/Zn superoxide dismutase (SOD1) cause a subset of cases of familial amyotrophic lateral sclerosis. Four lines of mice accumulating one of these mutant proteins (G37R) develop severe,Expand
Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase
TLDR
Cytochemical analysis revealed a severe reduction in succinate dehydrogenase and aconitase activities in the heart and, to a lesser extent, in other organs, which indicates that MnSOD is required for normal biological function of tissues by maintaining the integrity of mitochondrial enzymes susceptible to direct inactivation by superoxide. Expand
Aging, energy, and oxidative stress in neurodegenerative diseases
  • M. Beal
  • Biology, Medicine
  • Annals of neurology
  • 1995
TLDR
Potential therapeutic approaches include glutamate release inhibitors, excitatory amino acid antagonists, strategies to improve mitochondrial function, free radical scavengers, and trophic factors, which appear promising in experimental studies and are now being applied to human studies. Expand
Oxidative stress in neurodegenerative diseases.
TLDR
Elucidating the pathways important in the production of and defense from free radicals may be important in devising new pharmacologic strategies to slow or halt neuronal degeneration. Expand
A gain-of-function of an amyotrophic lateral sclerosis-associated Cu,Zn-superoxide dismutase mutant: An enhancement of free radical formation due to a decrease in Km for hydrogen peroxide.
TLDR
The ALS symptoms observed in G93A transgenic mice are not caused by the reduction of Cu,Zn-SOD activity with the mutant enzyme; rather, it is induced by a gain-of-function, an enhancement of the free radical-generating function. Expand
Calcium and Neuronal Injury in Alzheimer's Disease
  • M. Mattson
  • Chemistry, Medicine
  • Annals of the New York Academy of Sciences
  • 1994
Alzheimer's disease (AD) is defined by degeneration of specific populations of neurons and the presence of insoluble aggregates of cytoskeletal proteins and amyloid beta-peptide (A beta) withinExpand
The potential role of peroxynitrite in the vascular contractile and cellular energetic failure in endotoxic shock
TLDR
A role for peroxynitrite in the pathogenesis of cellular energetic failure and contractile dysfunction in endotoxin shock is suggested, along with previous data demonstrating protective effects of NO synthase inhibitors against the endotoxin‐induced contractile and energetic failure in the models of shock used in the current study. Expand
A metalloporphyrin superoxide dismutase mimetic protects against paraquat-induced endothelial cell injury, in vitro.
TLDR
These studies suggest that metalloporphyrin-based SOD mimetics may be useful agents in preventing injury and disease states associated with the generation of intracellular reactive oxygen species. Expand
A metalloporphyrin superoxide dismutase mimetic protects against paraquat-induced lung injury in vivo.
  • B. Day, J. Crapo
  • Chemistry, Medicine
  • Toxicology and applied pharmacology
  • 1996
TLDR
MnTBAP reduced lung injury as indicated by lower LDH levels, protein levels, and PMN influx in BAL fluid, which suggests that metalloporphyrins may be effective therapeutic agents against pathologies that involve overproduction of reactive oxygen species. Expand
...
1
2
3
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