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.
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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 |
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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
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