N-iminoethyl-L-lysine improves memory and reduces amyloid pathology in a transgenic mouse model of amyloid deposition

Neurochemistry International
Magali DumontMichael Lin

Abstract

A large body of evidence suggests the importance of inflammation and oxidative or nitrosative stress in Alzheimer's disease (AD) pathogenesis. Inflammatory stimuli upregulate transcription of inducible nitric oxide synthase (iNOS), which can lead to the production of nitric oxide and other reactive nitrogen species. We previously found that genetic deletion of iNOS in mice overexpressing the amyloid precursor protein (APP) and presenilin-1 (PS1) reduced mortality, nitrosative stress, amyloid plaque burden, microgliosis, astrocytosis, and peri-plaque tau phosphorylation. We therefore examined the effects of N6-(1-iminoethyl)-L-lysine (L-NIL), a pharmacological iNOS inhibitor, or d-NIL, its enantiomeric control, in a transgenic mouse model of amyloid deposition. Tg19959 mice carry human APP with two mutations and develop amyloid plaques and memory impairment starting at 3-4 months of age. Mice were given L-NIL or D-NIL in the drinking water from 1 month of age and assessed behaviorally and histopathologically at 8 months of age. We found that L-NIL administration reduced disinhibition in the elevated plus maze, improved spatial memory performance in the Morris water maze, and decreased cortical amyloid deposition as well as micro...Continue Reading

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Citations

Aug 28, 2012·Human Molecular Genetics·Magali DumontM Flint Beal
Aug 10, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Magali DumontFlint Beal
Feb 22, 2014·Human Molecular Genetics·Cliona StackMagali Dumont
Mar 1, 2012·Neuroscience and Biobehavioral Reviews·R LalondeC Strazielle
Dec 7, 2010·Free Radical Biology & Medicine·Magali Dumont, M Flint Beal
Sep 19, 2012·Mediators of Inflammation·Jan VítečekLukáš Kubala
Apr 27, 2012·PloS One·Carmen María Fernández-MartosFrancisco Javier Rodriguez
Nov 27, 2015·Nature Communications·Liqun WangMel B Feany
Jan 9, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Magali DumontM Flint Beal

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