Abstract
The amyloid-β(Aβ ) cascade hypothesis of Alzheimers disease (AD) has dominated research and subsequent therapeutic drug development for over two decades. Central to this hypothesis is the observation that Aβ is elevated in AD patients and that the disease is ultimately characterized by the central deposition of insoluble senile plaques. More recent evidence, however, suggests that the presence or absence of plaque is insufficient to fully account for the deleterious role of elevated Aβ in AD. Such studies support the basis for an alternate interpretation of the Aβ cascade hypothesis. Namely, that soluble oligomers of Aβ (i.e., ADDLs) accumulate and cause functional deficits prior to overt neuronal cell death or plaque deposition. Accordingly, the following review focuses on research describing the preparation and functional activity of ADDLs in vitro and in vivo. These studies provide the basis for an alternate, ADDL-based, view of the Aβ cascade hypothesis and accounts for the disconnect between plaque burden and cognitive deficits. Possible therapeutic approaches aimed at lowering ADDLs in AD patients are also considered.
Keywords: NMDA antagonist, amyloid precursor protein, long-term potentiation (LTP), NSAID, glycosaminoglycans
Current Topics in Medicinal Chemistry
Title: The Role of Amyloid-Beta Derived Diffusible Ligands (ADDLs) in Alzheimers Disease
Volume: 6 Issue: 6
Author(s): Susan M. Catalano, Elizabeth C. Dodson, Darrell A. Henze, Joseph G. Joyce, Grant A. Krafft and Gene G. Kinney
Affiliation:
Keywords: NMDA antagonist, amyloid precursor protein, long-term potentiation (LTP), NSAID, glycosaminoglycans
Abstract: The amyloid-β(Aβ ) cascade hypothesis of Alzheimers disease (AD) has dominated research and subsequent therapeutic drug development for over two decades. Central to this hypothesis is the observation that Aβ is elevated in AD patients and that the disease is ultimately characterized by the central deposition of insoluble senile plaques. More recent evidence, however, suggests that the presence or absence of plaque is insufficient to fully account for the deleterious role of elevated Aβ in AD. Such studies support the basis for an alternate interpretation of the Aβ cascade hypothesis. Namely, that soluble oligomers of Aβ (i.e., ADDLs) accumulate and cause functional deficits prior to overt neuronal cell death or plaque deposition. Accordingly, the following review focuses on research describing the preparation and functional activity of ADDLs in vitro and in vivo. These studies provide the basis for an alternate, ADDL-based, view of the Aβ cascade hypothesis and accounts for the disconnect between plaque burden and cognitive deficits. Possible therapeutic approaches aimed at lowering ADDLs in AD patients are also considered.
Export Options
About this article
Cite this article as:
Catalano M. Susan, Dodson C. Elizabeth, Henze A. Darrell, Joyce G. Joseph, Krafft A. Grant and Kinney G. Gene, The Role of Amyloid-Beta Derived Diffusible Ligands (ADDLs) in Alzheimers Disease, Current Topics in Medicinal Chemistry 2006; 6 (6) . https://dx.doi.org/10.2174/156802606776743066
DOI https://dx.doi.org/10.2174/156802606776743066 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Cognitive Impairment with Vascular Impairment and Degeneration
Current Neurovascular Research Calcitonin Gene-Related Family Peptides in Vascular Adaptations, Uteroplacental Circulation, and Fetal Growth
Current Vascular Pharmacology Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair
Current Pharmaceutical Design Editorial: Statins or Fibrates for the Primary Prevention of Stroke in the Elderly. Faith Makes Some Things Achievable, But Not A
Current Vascular Pharmacology Estrogen Receptor Polymorphisms: Significance to Human Physiology, Disease and Therapy
Recent Patents on DNA & Gene Sequences Editorial (Thematic Issue: Molecular Imaging in Dementia: From the State of the Art to the New Perspectives)
Current Alzheimer Research PCSK9 and LDLR The Yin-Yang in the Cellular Uptake of Cholesterol
Current Hypertension Reviews Critical Review of Malondialdehyde Analysis in Biological Samples
Current Pharmaceutical Analysis A Healthy Gut for a Healthy Brain: Preclinical, Clinical and Regulatory Aspects
Current Neuropharmacology Endothelial (Dys)Function in Lone Atrial Fibrillation
Current Pharmaceutical Design β3-Adrenergic Receptors: Really Relevant Targets for Anti-Obesity Drugs?
Current Medicinal Chemistry - Central Nervous System Agents The Hydrogen Peroxide and its Importance in Alzheimers and Parkinsons Disease
Current Medicinal Chemistry - Central Nervous System Agents Metabolic Syndrome and Cardiometabolic Risk Factors
Current Vascular Pharmacology The Use of Proteomics to Study Infectious Diseases
Infectious Disorders - Drug Targets Targeted Hydrolysis of Beta-Amyloid with Engineered Antibody Fragments
Current Alzheimer Research Brain Drug Delivery System: An Overview
Current Drug Therapy DNA Double Strand Breaks: A Common Theme in Neurodegenerative Diseases
Current Alzheimer Research Editorial (Thematic Issue: Overview of Immunotherapy in Alzheimer’s Disease (AD) and Mechanisms of IVIG Neuroprotection in Preclinical Models of AD)
Current Alzheimer Research Current Evidence and Future Perspectives on Anti-platelet and Statin Pharmacotherapy for Patients with Symptomatic Peripheral Arterial Disease
Current Vascular Pharmacology Clinical Use of Neurophysiological Biomarkers and Self-Assessment Scales to Predict and Monitor Treatment Response for Psychotic and Affective Disorders
Current Pharmaceutical Design