Abstract
Alzheimers disease (AD) is an intractable, neurodegenerative disease that appears to be brought about by both genetic and non-genetic factors. The neuropathology associated with AD is complex, although amyloid plaques composed of the β-amyloid peptide (Aβ) are hallmark neuropathological lesions of AD brain. Indeed, Aβ plays an early and central role in this disease. β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the initiating enzyme in Aβ genesis and BACE1 levels are elevated under a variety of conditions. Given the strong correlation between Aβ and AD, and the elevation of BACE1 in this disease, this enzyme is a prime drug target for inhibiting Aβ production in AD. However, nine years on from the initial identification of BACE1, and despite intense research, a number of key questions regarding BACE1 remain unanswered. Indeed, drug discovery and development for AD continues to be challenging. While current AD therapies temporarily slow cognitive decline, treatments that address the underlying pathologic mechanisms of AD are completely lacking. Here we review the basic biology of BACE1. We pay special attention to recent research that has provided some answers to questions such as those involving the identification of novel BACE1 substrates, the potential causes of BACE1 elevation and the putative function of BACE1 in health and disease. Our increasing understanding of BACE1 biology should aid the development of compounds that interfere with BACE1 expression and activity and may lead to the generation of novel therapeutics for AD.
Keywords: Alzheimer's, BACE1, β-secretase, Aβ, vascular disease, regulation, stress
Current Genomics
Title: The Basic Biology of BACE1: A Key Therapeutic Target for Alzheimers Disease
Volume: 8 Issue: 8
Author(s): R. Vassar and S. L. Cole
Affiliation:
Keywords: Alzheimer's, BACE1, β-secretase, Aβ, vascular disease, regulation, stress
Abstract: Alzheimers disease (AD) is an intractable, neurodegenerative disease that appears to be brought about by both genetic and non-genetic factors. The neuropathology associated with AD is complex, although amyloid plaques composed of the β-amyloid peptide (Aβ) are hallmark neuropathological lesions of AD brain. Indeed, Aβ plays an early and central role in this disease. β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the initiating enzyme in Aβ genesis and BACE1 levels are elevated under a variety of conditions. Given the strong correlation between Aβ and AD, and the elevation of BACE1 in this disease, this enzyme is a prime drug target for inhibiting Aβ production in AD. However, nine years on from the initial identification of BACE1, and despite intense research, a number of key questions regarding BACE1 remain unanswered. Indeed, drug discovery and development for AD continues to be challenging. While current AD therapies temporarily slow cognitive decline, treatments that address the underlying pathologic mechanisms of AD are completely lacking. Here we review the basic biology of BACE1. We pay special attention to recent research that has provided some answers to questions such as those involving the identification of novel BACE1 substrates, the potential causes of BACE1 elevation and the putative function of BACE1 in health and disease. Our increasing understanding of BACE1 biology should aid the development of compounds that interfere with BACE1 expression and activity and may lead to the generation of novel therapeutics for AD.
Export Options
About this article
Cite this article as:
Vassar R. and Cole L. S., The Basic Biology of BACE1: A Key Therapeutic Target for Alzheimers Disease, Current Genomics 2007; 8 (8) . https://dx.doi.org/10.2174/138920207783769512
DOI https://dx.doi.org/10.2174/138920207783769512 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Big Data in Cancer Research
Cancer is a significant threat to human life and health, remaining a highly aggressive killer. It is a leading cause of death worldwide and represents a crucial medical issue for humanity. However, in the past decade, the effectiveness of new synthetic anticancer agents has not matched the current clinical speculation. ...read more
Current Genomics in Cardiovascular Research
Cardiovascular diseases are the main cause of death in the world, in recent years we have had important advances in the interaction between cardiovascular disease and genomics. In this Research Topic, we intend for researchers to present their results with a focus on basic, translational and clinical investigations associated with ...read more
Related Journals
- 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
-
Mutation p.S335X in GATA4 Reduces its DNA Binding Affinity and Enhances Cell Apoptosis Associated with Ventricular Septal Defect
Current Molecular Medicine Knowing is Half the Battle: Targeting Virulence Factors of Group A Streptococcus for Vaccine and Therapeutics
Current Drug Targets Role of Angiotensin-1-Receptor Blockers In Cardiorenal Disease
Current Drug Therapy Emerging Therapies for Type 2 Diabetes
Current Drug Therapy Statins and epilepsy: preclinical studies, clinical trials and statin-anticonvulsant drug interactions
Current Drug Targets Cardiovascular Disease: What's All the AGE/RAGE About?
Cardiovascular & Hematological Disorders-Drug Targets Resveratrol and Analogues: A Review of Antioxidant Activity and Applications to Human Health
Recent Patents on Food, Nutrition & Agriculture Lifestyle Factors and Endothelial Function
Current Vascular Pharmacology Evaluation of the Pulmonary Veins and Left Atrial Volume using Multidetector Computed Tomography in Patients Undergoing Catheter Ablation for Atrial Fibrillation
Current Cardiology Reviews Biomarkers Associated with Stroke Risk in Atrial Fibrillation
Current Medicinal Chemistry MicroRNA-30 and 145 as Targets for the Treatment of Cardiovascular Diseases: Therapeutic Feasibility and Challenges
Current Pharmaceutical Design The Role of Coagulation and Fibrinolysis in the Pathogenesis of Acute Lung Injury
Current Respiratory Medicine Reviews Synthesis and Biological Evaluation of N-(Alkyl)-2-Thiophen-2-Ylacetamides Series As A New Class of Antitubercular Agents
Letters in Drug Design & Discovery Drug Carriers in Pharmaceutical Design: Promises and Progress
Current Pharmaceutical Design ABC Transporters in Extrahepatic Tissues: Pharmacological Regulation in Heart and Intestine
Current Medicinal Chemistry Ethnic Differences in Pharmacogenetically Relevant Genes
Current Drug Targets The Impact of Phytosterols on the Healthy and Diseased Brain
Current Medicinal Chemistry Gender Disparity in Lipid Target Achievements in High and Very High Atherosclerotic Cardiovascular Disease Risk Patients in the Arabian Gulf
Current Vascular Pharmacology Detection and Treatment of Alcohol-Induced Hypertension
Current Hypertension Reviews Combination of Fenofibrate with Non-Statin Drug Regimens
Current Pharmaceutical Design