Abstract
Major hallmarks of Alzheimers disease (AD) include brain deposition of the amyloid-β peptide (Aβ), which is proteolytically cleaved from a large Aβ precursor protein (APP) by β and β- secretases. A transmembrane aspartyl protease, β-APP cleaving enzyme (BACE1), has been recognized as the β-secretase. We review the structure and function of the BACE1 protein, and of 4129 bp of the 5-flanking region sequence of the BACE1 gene and its interaction with various transcription factors involved in cell signaling. The promoter region and 5-untranslated region (UTR) contain multiple transcription factor binding sites, such as AP-1, CREB and MEF2. A 91 bp fragment is the shortest region with significant reporter gene activity and constitutes the minimal promoter element for BACE1. The BACE1 promoter contains six unique functional domains and three structural domains of increasing sequence complexity as the “ATG” start codon is approached. Notably, the BACE1 gene promoter contains basal regulatory elements, inducible features and sites for regulation by various important transcription factors. Herein, we also discuss and speculate how the interaction of these transcription factors with the BACE1 promoter can modulate synaptic plasticity, neuronal apoptosis and oxidative stress, which are pertinent to the pathogenesis and progression of AD.
Keywords: mRNA EXPRESSION, inflammation, BACE1 homologue, cAMP response element-binding (CREB) sites, chloramphenicol acetyltransferase (CAT) reporter
Current Alzheimer Research
Title: Taking Down the Unindicted Co-Conspirators of Amyloid β-Peptidemediated Neuronal Death: Shared Gene Regulation of BACE1 and APP Genes Interacting with CREB, Fe65 and YY1 Transcription Factors
Volume: 3 Issue: 5
Author(s): Debomoy K. Lahiri, Yuan-Wen Ge, Jack T. Rogers, Kumar Sambamurti, Nigel H. Greig and Bryan Maloney
Affiliation:
Keywords: mRNA EXPRESSION, inflammation, BACE1 homologue, cAMP response element-binding (CREB) sites, chloramphenicol acetyltransferase (CAT) reporter
Abstract: Major hallmarks of Alzheimers disease (AD) include brain deposition of the amyloid-β peptide (Aβ), which is proteolytically cleaved from a large Aβ precursor protein (APP) by β and β- secretases. A transmembrane aspartyl protease, β-APP cleaving enzyme (BACE1), has been recognized as the β-secretase. We review the structure and function of the BACE1 protein, and of 4129 bp of the 5-flanking region sequence of the BACE1 gene and its interaction with various transcription factors involved in cell signaling. The promoter region and 5-untranslated region (UTR) contain multiple transcription factor binding sites, such as AP-1, CREB and MEF2. A 91 bp fragment is the shortest region with significant reporter gene activity and constitutes the minimal promoter element for BACE1. The BACE1 promoter contains six unique functional domains and three structural domains of increasing sequence complexity as the “ATG” start codon is approached. Notably, the BACE1 gene promoter contains basal regulatory elements, inducible features and sites for regulation by various important transcription factors. Herein, we also discuss and speculate how the interaction of these transcription factors with the BACE1 promoter can modulate synaptic plasticity, neuronal apoptosis and oxidative stress, which are pertinent to the pathogenesis and progression of AD.
Export Options
About this article
Cite this article as:
Lahiri K. Debomoy, Ge Yuan-Wen, Rogers T. Jack, Sambamurti Kumar, Greig H. Nigel and Maloney Bryan, Taking Down the Unindicted Co-Conspirators of Amyloid β-Peptidemediated Neuronal Death: Shared Gene Regulation of BACE1 and APP Genes Interacting with CREB, Fe65 and YY1 Transcription Factors, Current Alzheimer Research 2006; 3 (5) . https://dx.doi.org/10.2174/156720506779025224
DOI https://dx.doi.org/10.2174/156720506779025224 |
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
-
TRP Channels as Targets for Therapeutic Intervention in Obesity: Focus on TRPV1 and TRPM5
Current Topics in Medicinal Chemistry Norlichexanthone Isolated from Fungus P16 Promotes the Secretion and Expression of Adiponectin in Cultured ST-13 Adipocytes
Medicinal Chemistry Exosomes and Exosomal microRNAs in Age-associated Stroke
Current Vascular Pharmacology Imaging of Visceral Adipose Tissue: An Emerging Diagnostic Tool and Therapeutic Target
Current Drug Targets - Cardiovascular & Hematological Disorders HIV-1-Associated Dementia During HAART Therapy
Recent Patents on CNS Drug Discovery (Discontinued) Recent Trials for FTY720 (Fingolimod): A New Generation of Immunomodulators Structurally Similar to Sphingosine
Reviews on Recent Clinical Trials Statins and Ischaemia Reperfusion Injury: A Molecular Biological Review
Current Vascular Pharmacology Polymeric Nanomicelles of Soluplus® as a Strategy for Enhancing the Solubility, Bioavailability and Efficacy of Poorly Soluble Active Compounds
Current Nanomedicine Intracellular Amyloid β-Protein As a Therapeutic Target for Treating Alzheimers Disease
Current Alzheimer Research Nicotinamide and its Pharmacological Properties for Clinical Therapy
Drug Design Reviews - Online (Discontinued) COVID-19 Vaccines in Clinical Trials and their Mode of Action for Immunity against the Virus
Current Pharmaceutical Design Signaling Pathways Underpinning the Manifestations of Ionizing Radiation-Induced Bystander Effects
Current Molecular Pharmacology Circulating Biochemical Markers of Brain Damage in Infants Complicated by Ischemia Reperfusion Injury
Cardiovascular & Hematological Agents in Medicinal Chemistry Innovative formulations for controlled drug delivery to the lungs and the technical and toxicological challenges to overcome<sup>#</sup>
Current Pharmaceutical Design Thyroid Function and Obesity: From Mechanisms to the Benefits of Levothyroxine in Obese Patients
Endocrine, Metabolic & Immune Disorders - Drug Targets Metabotropic Glutamate Receptors as Therapeutic Targets for Cognitive Disorders
Current Topics in Medicinal Chemistry Protein Aggregation in Alzheimers Disease and Other Neoropathological Disorders
Current Alzheimer Research Spots, Blots, Peaks and Chips: Proteomic Approaches in Autoimmune Diseases
Current Pharmaceutical Design Animal Models Used for the Evaluation of Antiretroviral Therapies
Current HIV Research Proteomics Analysis of Liver Tissue of Labeo rohita
Current Proteomics