| Tolfenamic Acid Interrupts the De Novo Synthesis of the β-Amyloid Precursor Protein and Lowers Amyloid Beta Via a Transcriptional Pathway. | |
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MedLine Citation:
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PMID: 21557719 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Amyloid beta (Aβ) peptides are related to the pathogenesis of Alzheimer's disease (AD). The search for therapeutic strategies that lower these peptides has mainly focused on the proteolytic processing of the β-amyloid precursor protein (APP), and other post-transcriptional pathways. The transcription factor specificity protein 1 (Sp1) is vital for the regulation of several genes involved in AD including APP and the beta site APP cleaving enzyme 1 (BACE1). We have previously reported that tolfenamic acid promotes the degradation of Sp1 protein (SP1) in pancreatic human cancer cells and mice tumors. This study examines the ability of tolfenamic acid to reduce SP1 levels, and thereby decrease APP transcription and Aβ levels in rodent brains. Tolfenamic acid was administered by oral gavage to C57BL/6 mice at variable dosages and for different time periods. Results have shown that tolfenamic acid was able to down regulate brain protein levels of SP1, APP, and Aβ. These findings demonstrate that interference with upstream transcriptional pathways can lower pathogenic intermediates associated with AD, and thus tolfenamic acid represents a novel approach for the development of a therapeutic intervention for AD. |
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Authors:
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L I Adwan; R Basha; M Abdelrahim; G M Subaiea; N H Zawia |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-11 |
Journal Detail:
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Title: Current Alzheimer research Volume: - ISSN: 1875-5828 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101208441 Medline TA: Curr Alzheimer Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Fogarty Hall 41 Lower College Rd. Kingston, RI 02881; USA. nzawia@uri.edu. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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