Publication Date:
1998-09-22
Description:
Analysis of transgenic mice expressing familial amyotrophic lateral sclerosis (ALS)-linked mutations in the enzyme superoxide dismutase (SOD1) have shown that motor neuron death arises from a mutant-mediated toxic property or properties. In testing the disease mechanism, both elimination and elevation of wild-type SOD1 were found to have no effect on mutant-mediated disease, which demonstrates that the use of SOD mimetics is unlikely to be an effective therapy and raises the question of whether toxicity arises from superoxide-mediated oxidative stress. Aggregates containing SOD1 were common to disease caused by different mutants, implying that coaggregation of an unidentified essential component or components or aberrant catalysis by misfolded mutants underlies a portion of mutant-mediated toxicity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bruijn, L I -- Houseweart, M K -- Kato, S -- Anderson, K L -- Anderson, S D -- Ohama, E -- Reaume, A G -- Scott, R W -- Cleveland, D W -- NS 27036/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1998 Sep 18;281(5384):1851-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9743498" target="_blank"〉PubMed〈/a〉
Keywords:
Amyotrophic Lateral Sclerosis/*enzymology/genetics/pathology
;
Animals
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Astrocytes/enzymology/ultrastructure
;
Disease Progression
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Female
;
Humans
;
Hydrogen Peroxide/metabolism
;
Inclusion Bodies/enzymology/ultrastructure
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Male
;
Mice
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Mice, Transgenic
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Motor Neurons/enzymology/*pathology
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Mutation
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*Nerve Degeneration
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Oxidative Stress
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Superoxide Dismutase/genetics/*metabolism
;
Superoxides/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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