Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-1-14
pubmed:abstractText
Oxidative stress plays an important role in the pathogenesis of Alzheimer's disease. To determine which mechanisms cause the origin of oxidative damage, we analyzed enzymatic antioxidant defense (Cu/Zn-superoxide dismutase Cu/Zn-SOD, glutathione peroxidase GPx and glutathione reductase GR) and lipid peroxidation products malondialdehyde MDA and 4-hydroxynonenal HNE in two different APP transgenic mouse models at 3-4 and 12-15 months of age. No changes in any parameter were observed in brains from PDGF-APP695(SDL) mice, which have low levels of Abeta and no plaque load. In contrast, Thy1-APP751(SL) mice show high Abeta accumulation with aging and plaques from an age of 6 months. In brains of these mice, HNE levels were increased at 3 months (female transgenic mice) and at 12 months (both gender), that is, before and after plaque deposition, and the activity of Cu/Zn-SOD was reduced. Interestingly, beta-amyloidogenic cleavage of APP was increased in female Thy1-APP751(SL) mice, which also showed increased HNE levels with simultaneously reduced Cu/Zn-SOD activity earlier than male Thy1-APP751(SL) mice. Our results demonstrate that impaired Cu/Zn-SOD activity contributes to oxidative damage in Thy1-APP751(SL) transgenic mice, and these findings are closely linked to increased beta-amyloidogenic cleavage of APP.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0969-9961
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
89-99
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15649699-Aging, pubmed-meshheading:15649699-Aldehydes, pubmed-meshheading:15649699-Alzheimer Disease, pubmed-meshheading:15649699-Amyloid beta-Peptides, pubmed-meshheading:15649699-Amyloid beta-Protein Precursor, pubmed-meshheading:15649699-Animals, pubmed-meshheading:15649699-Brain, pubmed-meshheading:15649699-Disease Models, Animal, pubmed-meshheading:15649699-Female, pubmed-meshheading:15649699-Genetic Predisposition to Disease, pubmed-meshheading:15649699-Glutathione Peroxidase, pubmed-meshheading:15649699-Glutathione Reductase, pubmed-meshheading:15649699-Lipid Peroxidation, pubmed-meshheading:15649699-Male, pubmed-meshheading:15649699-Malondialdehyde, pubmed-meshheading:15649699-Mice, pubmed-meshheading:15649699-Mice, Transgenic, pubmed-meshheading:15649699-Oxidative Stress, pubmed-meshheading:15649699-Plaque, Amyloid, pubmed-meshheading:15649699-Sex Characteristics, pubmed-meshheading:15649699-Superoxide Dismutase, pubmed-meshheading:15649699-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
Impaired Cu/Zn-SOD activity contributes to increased oxidative damage in APP transgenic mice.
pubmed:affiliation
Department of Pharmacology, Biocentre, J.W. Goethe University of Frankfurt, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't