Does nitric oxide synthase contribute to the pathogenesis of Alzheimer's disease?: effects of beta-amyloid deposition on NOS in transgenic mouse brain with AD pathology.
Oxidative stress is a risk factor for Alzheimer's disease (AD) whose major hallmark includes brain depositions of the amyloid beta peptide (Abeta) derived from the beta-amyloid precursor protein (APP). Our aim was to determine whether or not excessive Abeta deposition would alter nitric oxide synthase (NOS) activity, and thereby affect NOS-mediated superoxide formation. We compared NOS activity in brain extracts between Tg mice (expressing APP Swedish double mutation plus presenilin [PS-1] and nontransgenic [nTg] mice. Five brain regions, including cerebral cortex, hippocampus, cerebellum, and striatum from both nTg and Tg mice showed a detectable level of neuronal (n) NOS activity. Cerebellar extracts from both nTg and Tg mice displayed the highest level of nNOS activity, which was fourfold higher than cortical extracts. Although there was an increase in nNOS activity in Tg brain extracts, this did not attain statistical significance. A similar result was obtained for inducible NOS levels. Our results suggest that excess levels of Abeta failed to both trigger NOS activity and change NOS levels.
Lahiri
D K
DK
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. dlahiri@iupui.edu
Chen
D
D
Ge
Y-W
YW
Farlow
M
M
Kotwal
G
G
Kanthasamy
A
A
Ingram
D K
DK
Greig
N H
NH
D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D012016:Reference Values
D016229:Amyloid beta-Peptides; C496320:NOS1 protein, human; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse