Abstract |
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.
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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 |
Journal | Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
(Neurotherapeutics)
Vol. 10
Issue 2
Pg. 340-53
(Apr 2013)
ISSN: 1878-7479 [Electronic] United States |
PMID | 23212232
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amyloid beta-Peptides
- Amyloid beta-Protein Precursor
- Cyclic N-Oxides
- Free Radical Scavengers
- Imidazoles
- N-p-nitrobenzoylpyrrolidinyl(4,5-dihydro-4,4,5,5-tetramethyl-3-oxido- 1H-imidazol-3-ium-1-oxyl-2-yl)
- Peptide Fragments
- Presenilin-1
- amyloid beta-protein (1-42)
- tau Proteins
- Superoxides
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Topics |
- 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)
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