Reduced antioxidant enzyme activity in brains of mice transgenic for human presenilin-1 with single or multiple mutations.
Alzheimer's disease-related mutations in the presenilin-1 gene (PS1) are leading to an elevated production of neurotoxic beta-amyloid 1-42 and may additionally enhance oxidative stress. Here, we provide in vivo evidence indicating that brains of transgenic mice expressing different human Alzheimer-linked PS1 mutations exhibit a reduced activity of two antioxidant enzymes. For this purpose, mice transgenic for human PS1 and for single and multiple PS1 mutations were generated. Mice with multiple PS1 mutations showed a significantly decreased activity of the antioxidant enzymes Cu/Zn superoxide dismutase and glutathione reductase already at an age of 3-4 months. As expected, this effect was less pronounced for the mice with a single PS1 mutation. By contrast, animals bearing normal human PS1 showed significantly elevated enzyme activities relative to non-transgenic littermate controls.
Leutner
S
S
Department of Pharmacology, Biocenter Niederursel, University of Frankfurt, Marie-Curie-Strasse 9, N 260, 60439 Frankfurt, Germany.
Czech
C
C
Schindowski
K
K
Touchet
N
N
Eckert
A
A
Müller
W E
WE
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis / Q000502:physiology; D009410:Nerve Degeneration / Q000378:metabolism; D053764:Presenilin-1; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D019076:Transgenes / Q000502:physiology
D000975:Antioxidants; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D005980:Glutathione Reductase