Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0002736 (
amyotrophic lateral sclerosis
)
19,048
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mutations in the enzyme copper/zinc superoxide dismutase-1 (SOD1) are associated with familial
amyotrophic lateral sclerosis
(FALS). The means by which the mutations cause FALS appears to be due to an adverse property of the mutant SOD1 protein that may involve increased generation of free radicals. We used in vivo microdialysis to measure the conversion of
4-hydroxybenzoic acid
to 3,4-dihydroxybenzoic acid (3,4-DHBA) as a measure of "hydroxyl radical-like" production in transgenic
amyotrophic lateral sclerosis
(
ALS
) mice with the G93A mutation as well as littermate controls. The conversion of
4-hydroxybenzoic acid
to 3,4-DHBA was significantly increased in the striatum of transgenic
ALS
mice at baseline but not in mice overexpressing wild-type human SOD1. Following administration of 3-nitropropionic acid 3,4-DHBA generation was significantly increased as compared with baseline, and the increase in the transgenic
ALS
mice was significantly greater than those in controls, whereas the increase in mice overexpressing wild-type human SOD1 was significantly attenuated. The present results provide in vivo evidence that expression of mutations in SOD1 can lead to increased generation of "hydroxyl radical-like" activity, which further implicates oxidative damage in the pathogenesis of
ALS
.
...
PMID:Elevated "hydroxyl radical" generation in vivo in an animal model of amyotrophic lateral sclerosis. 972 59
