Document Detail


A new chiral pyrrolyl α-nitronyl nitroxide radical attenuates β-amyloid deposition and rescues memory deficits in a mouse model of Alzheimer disease.
MedLine Citation:
PMID:  23212232     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The generation of reactive oxygen species causes cellular oxidative damage, and has been implicated in the etiology of Alzheimer's disease (AD). L-NNNBP, a new chiral pyrrolyl α-nitronyl nitroxide radical synthesized in our department, shows potential antioxidant effects. The purpose of this study was to investigate the protective effects of L-NNNBP on β-amyloid (Aβ) deposition and memory deficits in an AD model of APP/PS1 mice. In cultured cortical neurons, L-NNNBP acted as an antioxidant by quenching reactive oxygen species, inhibiting lipid peroxidation, nitrosative stress, and stimulating cellular antioxidant defenses. L-NNNBP inhibited cell apoptosis induced by Aβ exposure. In vivo treatment with L-NNNBP for 1 month induced a marked decrease in brain Aβ deposition and tau phosphorylation in the blinded study on APP/PS1 transgenic mice (1 mM in drinking water, initiated when the mice were 6 months old). The L-NNNBP-treated APP/PS1 mice showed decreased astrocyte activation and improved spatial learning and memory compared with the vehicle-treated APP/PS1 mice. These actions were more potent compared with that of curcumin, a natural product, and TEMPO, a nitroxide radical, which are used as free radical scavengers in clinics. These results proved that the newly synthesized L-NNNBP was an effective therapeutic agent for the prevention and treatment of AD.
Authors:
Tian-Yao Shi; Da-Qing Zhao; Hai-Bo Wang; Shufang Feng; Shui-Bing Liu; Jiang-Hao Xing; Yang Qu; Peng Gao; Xiao-Li Sun; Ming-Gao Zhao
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics     Volume:  10     ISSN:  1878-7479     ISO Abbreviation:  Neurotherapeutics     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-15     Completed Date:  2013-10-24     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  101290381     Medline TA:  Neurotherapeutics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  340-53     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / drug therapy*,  psychology*
Amyloid beta-Peptides / antagonists & inhibitors,  metabolism*,  toxicity
Amyloid beta-Protein Precursor / metabolism
Animals
Cell Survival / drug effects
Cells, Cultured
Cyclic N-Oxides / pharmacology*
Fluorescent Antibody Technique
Free Radical Scavengers / pharmacology
Humans
Imidazoles / pharmacology*
In Situ Nick-End Labeling
Lipid Peroxidation / drug effects
Maze Learning / drug effects
Memory Disorders / prevention & control*,  psychology*
Mice
Mice, Transgenic
Microsomes, Liver / drug effects,  metabolism
Neurons / drug effects
Peptide Fragments / antagonists & inhibitors,  toxicity
Plaque, Amyloid / prevention & control*
Presenilin-1 / metabolism
Superoxides / metabolism
tau Proteins / metabolism
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Amyloid beta-Protein Precursor; 0/Cyclic N-Oxides; 0/Free Radical Scavengers; 0/Imidazoles; 0/N-p-nitrobenzoylpyrrolidinyl(4,5-dihydro-4,4,5,5-tetramethyl-3-oxido- 1H-imidazol-3-ium-1-oxyl-2-yl); 0/Peptide Fragments; 0/Presenilin-1; 0/amyloid beta-protein (1-42); 0/tau Proteins; 11062-77-4/Superoxides
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Aggregation-enhanced emission and efficient electroluminescence of tetraphenylethene-cored luminogen...
Next Document:  Palladium ketonyl carboxylate complexes - potential models of polynuclear intermediates in olefin ox...