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

Overview

MeSH Major

  • Alzheimer Disease
  • Gene Deletion
  • 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.

publication date

  • November 7, 2005

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2213235

Digital Object Identifier (DOI)

  • 10.1084/jem.20051529

PubMed ID

  • 16260491

Additional Document Info

start page

  • 1163

end page

  • 9

volume

  • 202

number

  • 9