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Does Nitric Oxide Synthase Contribute to the Pathogenesis of Alzheimer's Disease?
Author(s) -
LAHIRI D K.,
CHEN D,
GE YW,
FARLOW M,
KOTWAL G,
KANTHASAMY A,
INGRAM D K.,
GREIG N H.
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1299.117
Subject(s) - nitric oxide synthase , presenilin , hippocampus , oxidative stress , chemistry , nitric oxide , pathogenesis , medicine , endocrinology , cerebellum , alzheimer's disease , cerebral cortex , amyloid precursor protein , amyloid beta , striatum , amyloid (mycology) , biology , biochemistry , peptide , dopamine , disease , inorganic chemistry
A bstract : Oxidative stress is a risk factor for Alzheimer's disease (AD) whose major hallmark includes brain depositions of the amyloid beta peptide (Aβ) derived from the β‐amyloid precursor protein (APP). Our aim was to determine whether or not excessive Aβ 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 Aβ failed to both trigger NOS activity and change NOS levels.