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Protection from Alzheimer's-like disease in the mouse by genetic ablation of inducible nitric oxide synthase.

TitleProtection from Alzheimer's-like disease in the mouse by genetic ablation of inducible nitric oxide synthase.
Publication TypeJournal Article
Year of Publication2005
AuthorsNathan C, Calingasan N, Nezezon J, Ding A, M Lucia S, La Perle K, Fuortes M, Lin M, Ehrt S, Kwon NSoo, Chen J, Vodovotz Y, Kipiani K, M Beal F
JournalJ Exp Med
Volume202
Issue9
Pagination1163-9
Date Published2005 Nov 07
ISSN0022-1007
KeywordsAlzheimer Disease, Animals, Brain, Crosses, Genetic, Disease Models, Animal, Gene Deletion, Humans, Inbreeding, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Nitric Oxide Synthase Type II
Abstract

Brains from subjects who have Alzheimer's disease (AD) express inducible nitric oxide synthase (iNOS). We tested the hypothesis that iNOS contributes to AD pathogenesis. Immunoreactive iNOS was detected in brains of mice with AD-like disease resulting from transgenic expression of mutant human beta-amyloid precursor protein (hAPP) and presenilin-1 (hPS1). We bred hAPP-, hPS1-double transgenic mice to be iNOS(+/+) or iNOS(-/-), and compared them with a congenic WT strain. Deficiency of iNOS substantially protected the AD-like mice from premature mortality, cerebral plaque formation, increased beta-amyloid levels, protein tyrosine nitration, astrocytosis, and microgliosis. Thus, iNOS seems to be a major instigator of beta-amyloid deposition and disease progression. Inhibition of iNOS may be a therapeutic option in AD.

DOI10.1084/jem.20051529
Alternate JournalJ Exp Med
PubMed ID16260491
PubMed Central IDPMC2213235
Grant ListR01 AG019520 / AG / NIA NIH HHS / United States
R01 AG020729 / AG / NIA NIH HHS / United States
AG19520 / AG / NIA NIH HHS / United States
AG20729 / AG / NIA NIH HHS / United States

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