title: Protection from Alzheimer's-like disease in the mouse by genetic ablation of inducible nitric oxide synthase.
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.
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Nathan
authors.forename: Noel
authors.initials: N
authors.lastname: Calingasan
authors.forename: Jon
authors.initials: J
authors.lastname: Nezezon
authors.forename: Aihao
authors.initials: A
authors.lastname: Ding
authors.forename: M Scott
authors.initials: MS
authors.lastname: Lucia
authors.forename: Krista
authors.initials: K
authors.lastname: La Perle
authors.forename: Michele
authors.initials: M
authors.lastname: Fuortes
authors.forename: Michael
authors.initials: M
authors.lastname: Lin
authors.forename: Sabine
authors.initials: S
authors.lastname: Ehrt
authors.forename: Nyoun Soo
authors.initials: NS
authors.lastname: Kwon
authors.forename: Junyu
authors.initials: J
authors.lastname: Chen
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
authors.forename: Khatuna
authors.initials: K
authors.lastname: Kipiani
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D017353:Gene Deletion; D006801:Humans; D007178:Inbreeding; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency / Q000235:genetics*
chemical_list: D052247:Nitric Oxide Synthase Type II