| Pro-oxidant diet enhances β/γ secretase-mediated APP processing in APP/PS1 transgenic mice. | |
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MedLine Citation:
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PMID: 20724034 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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The etiology of Alzheimer's disease (AD) is complex with oxidative stress being a possible contributory factor to pathogenesis and disease progression. TASTPM transgenic mice expressing familial AD-associated amyloid precursor protein (APPswe) and presenilin transgenes (PS1M146V) show increased brain amyloid beta (Aβ) levels and Aβ plaques from 3 months. We tested if enhancing oxidative stress through diet would accelerate Aβ-related pathology. TASTPM were fed a pro-oxidant diet for 3 months resulting in increased brain levels of protein carbonyls, increased Nrf2, and elevated concentrations of glutathione (GSH). The diet increased both amyloid precursor protein (APP) and Aβ in the cortex of TASTPM but did not alter Aβ plaque load, presenilin 1, or β-secretase (BACE1) expression. TASTPM cortical neurons were cultured under similar pro-oxidant conditions resulting in increased levels of APP and Aβ likely as a result of enhanced β/γ secretase processing of APP. Thus, pro-oxidant conditions increase APP levels and enhance BACE1-mediated APP processing and in doing so might contribute to pathogenesis in AD. |
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Authors:
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Fahd Choudhry; David R Howlett; Jill C Richardson; Paul T Francis; Robert J Williams |
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Publication Detail:
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Type: Journal Article Date: 2010-08-17 |
Journal Detail:
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Title: Neurobiology of aging Volume: 33 ISSN: 1558-1497 ISO Abbreviation: Neurobiol. Aging Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-03-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8100437 Medline TA: Neurobiol Aging Country: United States |
Other Details:
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Languages: eng Pagination: 960-8 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Wolfson Centre for Age-Related Diseases, King's College London, London, UK. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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