Abstract
As the most common neurodegenerative disease, therapeutic avenues for the treatment and prevention of Alzheimer’s Disease are highly sought after. The aspartic protease BACE1 is the initiator enzyme for the formation of Aβ, a major constituent of amyloid plaques that represent one of the hallmark pathological features of this disorder. Thus, targeting BACE1 for disease-modifying AD therapies represents a rationale approach. The collective knowledge acquired from investigations of BACE1 deletion mutants and characterization of BACE1 substrates has downstream significance not only for the discovery of AD drug therapies but also for predicting side effects of BACE1 inhibition. Here we discuss the identification and validation of BACE1 as the β-secretase implicated in AD, in addition to information regarding BACE1 cell biology, localization, substrates and potential physiological functions derived from BACE1 knockout models.
Keywords: Alzheimer’s disease, BACE1, beta-secretase.
Current Alzheimer Research
Title:The Normal and Pathologic Roles of the Alzheimer's β-secretase, BACE1
Volume: 11 Issue: 5
Author(s): Patty C. Kandalepas and Robert Vassar
Affiliation:
Keywords: Alzheimer’s disease, BACE1, beta-secretase.
Abstract: As the most common neurodegenerative disease, therapeutic avenues for the treatment and prevention of Alzheimer’s Disease are highly sought after. The aspartic protease BACE1 is the initiator enzyme for the formation of Aβ, a major constituent of amyloid plaques that represent one of the hallmark pathological features of this disorder. Thus, targeting BACE1 for disease-modifying AD therapies represents a rationale approach. The collective knowledge acquired from investigations of BACE1 deletion mutants and characterization of BACE1 substrates has downstream significance not only for the discovery of AD drug therapies but also for predicting side effects of BACE1 inhibition. Here we discuss the identification and validation of BACE1 as the β-secretase implicated in AD, in addition to information regarding BACE1 cell biology, localization, substrates and potential physiological functions derived from BACE1 knockout models.
Export Options
About this article
Cite this article as:
Kandalepas C. Patty and Vassar Robert, The Normal and Pathologic Roles of the Alzheimer's β-secretase, BACE1, Current Alzheimer Research 2014; 11 (5) . https://dx.doi.org/10.2174/1567205011666140604122059
DOI https://dx.doi.org/10.2174/1567205011666140604122059 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
- 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
-
Metallothioneins and Synthetic Metal Chelators as Potential Therapeutic Agents for Removal of Aberrant Metal Ions from Metal-Aβ Species
Mini-Reviews in Medicinal Chemistry Characterization of LC-HCC Fusion Protein of Botulinum Neurotoxin Type A
Protein & Peptide Letters Hydroxamic Acids as Pharmacological Agents: An Update
Medicinal Chemistry Reviews - Online (Discontinued) CDK Inhibitors Induce Mitochondria-mediated Apoptosis Through the Activation of Polyamine Catabolic Pathway in LNCaP, DU145 and PC3 Prostate Cancer Cells
Current Pharmaceutical Design Recent Patents on Live Bacteria and their Products as Potential Anticancer Agents
Recent Patents on Anti-Cancer Drug Discovery Mechanisms of Tubulin Binding Ligands to Target Cancer Cells: Updates on their Therapeutic Potential and Clinical Trials
Current Cancer Drug Targets Can Tea Consumption be a Safe and Effective Therapy Against Diabetes Mellitus-Induced Neurodegeneration?
Current Neuropharmacology Rationale for the Development of Cholinesterase Inhibitors as Anti- Alzheimer Agents
Current Pharmaceutical Design Vasoactive Intestinal Peptide Receptors: A Molecular Target in Breast and Lung Cancer
Current Pharmaceutical Design The Paradox of Oestradiol-Induced Breast Cancer Cell Growth and Apoptosis
Current Signal Transduction Therapy Current Approaches for the Treatment with Thyroid Hormone Analogs
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Mitochondrial VDAC1: Function in Cell Life and Death and a Target for Cancer Therapy
Current Medicinal Chemistry Anesthesia, Calcium Homeostasis and Alzheimers Disease
Current Alzheimer Research Review: The Role of Radiolabeled DOTA-Conjugated Peptides for Imaging and Treatment of Childhood Neuroblastoma
Current Radiopharmaceuticals An Up-date of Olive Oil Phenols in Inflammation and Cancer: Molecular Mechanisms and Clinical Implications
Current Medicinal Chemistry The Translocator Protein 18 kDa (TSPO) and Its Role in Mitochondrial Biology and Psychiatric Disorders
Mini-Reviews in Medicinal Chemistry Glial Cells – The Key Elements of Alzheimer´s Disease
Current Alzheimer Research Proteases as Anti-Cancer Targets - Molecular and Biological Basis for Development of Inhibitor-Like Drugs Against Cancer
Anti-Cancer Agents in Medicinal Chemistry Targeting the PI3K/Akt/mTOR Axis by Apigenin for Cancer Prevention
Anti-Cancer Agents in Medicinal Chemistry Pharmacological Applications of Diphenylamine and Its Derivative as Potent Bioactive Compound: A Review
Current Bioactive Compounds