Abstract
Amyloid beta (Aβ) peptides are related to the pathogenesis of Alzheimers 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 downregulate 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.
Keywords: Alzheimer's disease, amyloid beta, APP, Sp1, tolfenamic acid, transcription, APP cleaving enzyme 1, Abeta Protein Levels, migraine headaches
Current Alzheimer Research
Title: Tolfenamic Acid Interrupts the De Novo Synthesis of the β-Amyloid Precursor Protein and Lowers Amyloid Beta Via a Transcriptional Pathway
Volume: 8 Issue: 4
Author(s): L. I. Adwan, R. Basha, M. Abdelrahim, G. M. Subaiea and N. H. Zawia
Affiliation:
Keywords: Alzheimer's disease, amyloid beta, APP, Sp1, tolfenamic acid, transcription, APP cleaving enzyme 1, Abeta Protein Levels, migraine headaches
Abstract: Amyloid beta (Aβ) peptides are related to the pathogenesis of Alzheimers 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 downregulate 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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Cite this article as:
I. Adwan L., Basha R., Abdelrahim M., M. Subaiea G. and H. Zawia N., Tolfenamic Acid Interrupts the De Novo Synthesis of the β-Amyloid Precursor Protein and Lowers Amyloid Beta Via a Transcriptional Pathway, Current Alzheimer Research 2011; 8 (4) . https://dx.doi.org/10.2174/156720511795745285
DOI https://dx.doi.org/10.2174/156720511795745285 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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