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
-
Postprandial Glucose - A Potential Therapeutic Target to Reduce Cardiovascular Mortality
Current Vascular Pharmacology GPER/GPR30 and Regulation of Vascular Tone and Blood Pressure
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) The Role of Diet in Patients with Metabolic Syndrome
Current Medicinal Chemistry Is there Sex-related Outcome Difference According to oral P2Y12 Inhibitors in Patients with Acute Coronary Syndromes? A Systematic Review and Meta-Analysis of 107,126 Patients
Current Vascular Pharmacology Vasorelaxant and Antihypertensive Effects of <i>Mentha pulegium</i> L. in Rats: An In vitro and In vivo Approach
Endocrine, Metabolic & Immune Disorders - Drug Targets Avian Genomes: Important Resources for Understanding Vertebrate Biology
Current Genomics AAV Vectorization of DSB-mediated Gene Editing Technologies
Current Gene Therapy Lifestyle Choices and Endothelial Function: Risk and Relevance
Current Vascular Pharmacology Emerging Drugs and Indications for Cardio-Metabolic Disorders in People with Severe Mental Illness
Current Pharmaceutical Design Epigenetics in Vascular Disease – Therapeutic Potential of New Agents
Current Vascular Pharmacology Daily Melatonin Administration Attenuates Age-Dependent Disturbances of Cardiovascular Rhythms
Current Aging Science MicroRNA in Aging: From Discovery to Biology
Current Genomics Current Application of Cyclosporine A to Investigate Skeletal Muscle Adaptation
Current Enzyme Inhibition Twin-to-Twin Transfusion Syndrome: From Placental Anastomoses to Long-Term Neurodevelopmental Outcome
Current Pediatric Reviews Racial Differences in Gray Matter Integrity by Diffusion Tensor in Black and White Octogenarians
Current Alzheimer Research Statins and Inflammation in Cardiovascular Disease
Current Pharmaceutical Design The Role of Novel Biomarkers of Cardiovascular Disease in Chronic Kidney Disease: Focus on Adiponectin and Leptin
Current Cardiology Reviews Rationalizing the Study of Plants for the Treatment of Oral Pain
Current Chemical Biology Biomarkers in Systemic Sclerosis-Related Pulmonary Arterial Hypertension
Current Vascular Pharmacology Diabetic Vasculopathy and the Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 (LOX-1)
Current Diabetes Reviews