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

Carl Nathan*, Noel Calingasan, Jon Nezezon, Aihao Ding, M. Scott Lucia, Krista La Perle, Michele Fuortes, Michael Lin, Sabine Ehrt, Soo Kwon Nyoun, Junyu Chen, Yoram Vodovotz, Khatuna Kipiani, M. Flint Beal

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

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 β-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 β-amyloid levels, protein tyrosine nitration, astrocytosis, and microgliosis. Thus, iNOS seems to be a major instigator of β-amyloid deposition and disease progression. Inhibition of iNOS may be a therapeutic option in AD. JEM

Original languageEnglish
Pages (from-to)1163-1169
Number of pages7
JournalJournal of Experimental Medicine
Volume202
Issue number9
DOIs
StatePublished - 7 Nov 2005
Externally publishedYes

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