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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Retinoids in Cancer Chemoprevention
Current Cancer Drug Targets The Changing Face of Tobacco Use Among United States Youth
Current Drug Abuse Reviews Conditionally Replicating Adenoviruses for Cancer Treatment
Current Cancer Drug Targets Green Tea Polyphenols as Proteasome Inhibitors: Implication in Chemoprevention
Current Cancer Drug Targets Editorial
Recent Patents on Inflammation & Allergy Drug Discovery Natural Product as Substrates of ABC Transporters: A Review
Recent Patents on Anti-Cancer Drug Discovery Cell Responses to Oxidative Stressors
Current Pharmaceutical Design CD40L - A Multipotent Molecule for Tumor Therapy
Endocrine, Metabolic & Immune Disorders - Drug Targets Metabolomics: A Revolution for Novel Cancer Marker Identification
Combinatorial Chemistry & High Throughput Screening Regulation of Cell Migration and Invasion by Specific Modules of uPA: Mechanistic Insights and Specific Inhibitors
Current Drug Targets Editorial [Hot topic: Cell Adhesion Molecules: Structure, Function, Drug Design, and Biomaterials (Executive Editor: Seetharama D. Satyanarayanajois)]
Current Pharmaceutical Design Dihydrofolate Reductase Gene Variations in Susceptibility to Disease and Treatment Outcomes
Current Genomics In Vivo Target Validation: Methodology and Case Studies on the Janus Kinase Tyk2
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry When Neighbors Talk: Colon Cancer Cell Invasion and Tumor Microenvironment Myofibroblasts
Current Drug Targets AMPK: Therapeutic Target for Diabetes and Cancer Prevention
Current Pharmaceutical Design Serum α-1 Acid Glycoprotein is a Biomarker for the Prediction of Targeted Therapy Resistance in Advanced EGFR-positive Lung Adenocarcinoma
Combinatorial Chemistry & High Throughput Screening Application of Proteome Analysis to the Assessment of Prognosis and Response Prediction in Clinical Oncology
Current Cancer Drug Targets The Membrane-targeted Alkylphosphocholine Erufosine Interferes with Survival Signals from the Extracellular Matrix
Anti-Cancer Agents in Medicinal Chemistry The Sam Domain of EphA2 Receptor and its Relevance to Cancer: A Novel Challenge for Drug Discovery?
Current Medicinal Chemistry Assembly of Quinoline, Triazole and Oxime Ether in a Single Molecular Entity: A Greener and One-pot Synthesis of Novel Oximes as Potential Cytotoxic Agents
Letters in Drug Design & Discovery