| A New Chiral Pyrrolyl α-Nitronyl Nitroxide Radical Attenuates β-Amyloid Deposition and Rescues Memory Deficits in a Mouse Model of Alzheimer Disease. | |
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MedLine Citation:
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PMID: 23212232 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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:
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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:
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Type: JOURNAL ARTICLE Date: 2012-12-5 |
Journal Detail:
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Title: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics Volume: - ISSN: 1878-7479 ISO Abbreviation: Neurotherapeutics Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101290381 Medline TA: Neurotherapeutics Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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