Publication Date:
2000-01-05
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Estevez, A G -- Crow, J P -- Sampson, J B -- Reiter, C -- Zhuang, Y -- Richardson, G J -- Tarpey, M M -- Barbeito, L -- Beckman, J S -- R01 HL58209/HL/NHLBI NIH HHS/ -- R01 NS33291/NS/NINDS NIH HHS/ -- R01 NS36761/NS/NINDS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2498-500.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617463" target="_blank"〉PubMed〈/a〉
Keywords:
Amyotrophic Lateral Sclerosis/drug therapy/*enzymology/genetics/pathology
;
Animals
;
*Apoptosis
;
Brain-Derived Neurotrophic Factor/pharmacology
;
Cells, Cultured
;
Chelating Agents/pharmacology
;
Copper/metabolism
;
Fluoresceins/metabolism
;
Liposomes
;
Motor Neurons/*cytology/metabolism
;
Mutation
;
Nitrates/metabolism
;
Nitric Oxide/*metabolism
;
Nitric Oxide Synthase/antagonists & inhibitors/metabolism
;
Nitric Oxide Synthase Type I
;
Oxidation-Reduction
;
Rats
;
Superoxide Dismutase/chemistry/genetics/*metabolism/toxicity
;
Superoxides/metabolism
;
Zinc/*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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