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
-
Serum Amyloid A and Its Potential Physiological / Pathological Functions - an Overview of Patents
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Melatonin in Pregnancy: Effects on Brain Development and CNS Programming Disorders
Current Pharmaceutical Design Pathophysiology and Pharmacological Targeting of Tumor-Induced Bone Disease: Current Status and Emerging Therapeutic Interventions
Current Medicinal Chemistry The Prognostic Impact of Pleural Invasion in Lung Cancer According to the UICC Classification
Current Respiratory Medicine Reviews <i>In Vivo</i> Antitumor, Pharmacological and Toxicological Study of Pyrimido[ 4′,5′:4,5] thieno(2,3-b)quinoline with 9-hydroxy-4-(3-diethylaminopropylamino) and 8-methoxy-4-(3-diethylaminopropylamino) Substitutions
Anti-Cancer Agents in Medicinal Chemistry Placebos Used in Clinical Trials for Chinese Herbal Medicine
Recent Patents on Inflammation & Allergy Drug Discovery Inhibiting HSP90 to Treat Cancer: A Strategy in Evolution
Current Molecular Medicine Multifunctional Nanomedicine Platform for Cancer Specific Delivery of siRNA by Superparamagnetic Iron Oxide Nanoparticles-Dendrimer Complexes
Current Drug Delivery Cancer Stem Cells: Current Status and Therapeutic Implications in Cancer Therapy-A New Paradigm
Current Stem Cell Research & Therapy Hydrogen Sulfide-Based Therapies: Focus on H2S Releasing NSAIDs
Inflammation & Allergy - Drug Targets (Discontinued) The Blood-Brain Barrier: Its Influence in the Treatment of Brain Tumors Metastases
Current Cancer Drug Targets Subject Index to Volume 10
Protein & Peptide Letters Antitumor Activity and Structure-Activity Relationship of Diterpenoids with a Dehydroabietyl Skeleton
Combinatorial Chemistry & High Throughput Screening A QSAR Study on a Series of Indolin-2-Ones Acting as Non-Receptor Src Tyrosine Kinase Inhibitors
Letters in Drug Design & Discovery Insights into the Role of Fc Gamma Receptors (FcγRs) Genetic Variations in Monoclonal Antibody-Based Anti-Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Potential Therapeutic Agents Against Par-4 Target for Cancer Treatment: Where Are We Going?
Current Drug Targets An Overview of Phytochemical and Pharmacological Profile of <i>Morus alba</i> Linn
Current Bioactive Compounds Novel Molecular-Targeted Therapeutics for the Treatment of Cancer
Anti-Cancer Agents in Medicinal Chemistry Transactivation of ErbB Receptors by Leptin in the Cardiovascular System: Mechanisms, Consequences and Target for Therapy
Current Pharmaceutical Design Development of Genomics-Based Gene Expression Signature Biomarkers in Oncology and Toxicology to Facilitate Drug Discovery and Translational Medicine
Current Bioinformatics