Abstract
Alzheimers disease (AD) is a neurodegenerative disorder characterized by the deposition of beta amyloid (Aβ) protein and the formation of neurofibrillary tangles. In addition, there is an increase of inflammatory proteins in the brains of AD patients. Epidemiological studies, indicating that non-steroidal anti-inflammatory drugs (NSAIDs) decrease the risk of developing AD, have encouraged the study on the role of inflammation in AD. The best-characterized action of most NSAIDs is the inhibition of cyclooxygenase (COX). The expression of the constitutively expressed COX-1 and the inflammatory induced COX-2 has been intensively investigated in AD brain and different disease models for AD. Despite these studies, clinical trials with NSAIDs or selective COX-2 inhibitors showed little or no effect on clinical progression of AD. The expression levels of COX-1 and COX-2 change in the different stages of AD pathology. In an early stage, when low-fibrillar Aβ deposits are present and only very few neurofibrillary tangles are observed in the cortical areas, COX-2 is increased in neurons. The increased neuronal COX-2 expression parallels and colocalizes with the expression of cell cycle proteins. COX-1 is primarily expressed in microglia, which are associated with fibrillar Aβ deposits. This suggests that in AD brain COX-1 and COX-2 are involved in inflammatory and regenerating pathways respectively. In this review we will discuss the role of COX-1 and COX-2 in the different stages of AD pathology. Understanding the physiological and pathological role of cyclooxygenase in AD pathology may facilitate the design of therapeutics for the treatment or prevention of AD.
Keywords: Alzheimer's disease, β amyloid, cell cycle proteins, cyclooxygenase-1, cyclooxygenase-2, microglia, neuroinflammation, neuron, non-steroidal anti-inflammatory drugs
Current Pharmaceutical Design
Title: Cyclooxygenase-1 and -2 in the Different Stages of Alzheimers Disease Pathology
Volume: 14 Issue: 14
Author(s): J. J.M. Hoozemans, J. M. Rozemuller, E. S. van Haastert, R. Veerhuis and P. Eikelenboom
Affiliation:
Keywords: Alzheimer's disease, β amyloid, cell cycle proteins, cyclooxygenase-1, cyclooxygenase-2, microglia, neuroinflammation, neuron, non-steroidal anti-inflammatory drugs
Abstract: Alzheimers disease (AD) is a neurodegenerative disorder characterized by the deposition of beta amyloid (Aβ) protein and the formation of neurofibrillary tangles. In addition, there is an increase of inflammatory proteins in the brains of AD patients. Epidemiological studies, indicating that non-steroidal anti-inflammatory drugs (NSAIDs) decrease the risk of developing AD, have encouraged the study on the role of inflammation in AD. The best-characterized action of most NSAIDs is the inhibition of cyclooxygenase (COX). The expression of the constitutively expressed COX-1 and the inflammatory induced COX-2 has been intensively investigated in AD brain and different disease models for AD. Despite these studies, clinical trials with NSAIDs or selective COX-2 inhibitors showed little or no effect on clinical progression of AD. The expression levels of COX-1 and COX-2 change in the different stages of AD pathology. In an early stage, when low-fibrillar Aβ deposits are present and only very few neurofibrillary tangles are observed in the cortical areas, COX-2 is increased in neurons. The increased neuronal COX-2 expression parallels and colocalizes with the expression of cell cycle proteins. COX-1 is primarily expressed in microglia, which are associated with fibrillar Aβ deposits. This suggests that in AD brain COX-1 and COX-2 are involved in inflammatory and regenerating pathways respectively. In this review we will discuss the role of COX-1 and COX-2 in the different stages of AD pathology. Understanding the physiological and pathological role of cyclooxygenase in AD pathology may facilitate the design of therapeutics for the treatment or prevention of AD.
Export Options
About this article
Cite this article as:
Hoozemans J.M. J., Rozemuller M. J., van Haastert S. E., Veerhuis R. and Eikelenboom P., Cyclooxygenase-1 and -2 in the Different Stages of Alzheimers Disease Pathology, Current Pharmaceutical Design 2008; 14 (14) . https://dx.doi.org/10.2174/138161208784480171
DOI https://dx.doi.org/10.2174/138161208784480171 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Editorial (Hot Topic : Computational Prediction of Drug-Target Interactions in Medicinal Chemistry)
Current Topics in Medicinal Chemistry α-Synuclein Ubiquitination and Novel Therapeutic Targets for Parkinson's Disease
CNS & Neurological Disorders - Drug Targets Anti-oxidant and Antiproliferative Activities of Mongolian Medicinal Plant Extracts and Structure Isolation of Gnetin-H Compound
Medicinal Chemistry Synthesis of Propargylamines by Cross-Dehydrogenative Coupling
Current Green Chemistry Peripheral Kynurenine Metabolism in Focal Dystonia
Medicinal Chemistry The Effects of Dietary Supplements that Overactivate the Nrf2/ARE System
Current Medicinal Chemistry Flavonoids and the Brain: Evidences and Putative Mechanisms for a Protective Capacity
Current Neuropharmacology Highly Organized Nanostructures for Brain Drug Delivery - New Hope or Just a Fad?
CNS & Neurological Disorders - Drug Targets Potential Roles of Selenium and Selenoproteins in the Prevention of Alzheimer's Disease
Current Topics in Medicinal Chemistry Reorganizing Metals: the Use of Chelating Compounds as Potential Therapies for Metal-Related Neurodegenerative Disease
Current Topics in Medicinal Chemistry Viral Induced Oxidative and Inflammatory Response in Alzheimer’s Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach
Current Neuropharmacology MicroRNAs Involved in Oxidative Stress Processes Regulating Physiological and Pathological Responses
MicroRNA The Forkhead Transcription Factor FOXO3a Controls Microglial Inflammatory Activation and Eventual Apoptotic Injury through Caspase 3
Current Neurovascular Research The Atypical Cannabinoid O-1602: Targets, Actions, and the Central Nervous System
Central Nervous System Agents in Medicinal Chemistry Structurally Unprecedented Metabolites from Marine Sponges
Current Organic Chemistry Lipoprotein Like Nanoparticles Used in Drug and Gene Delivery
Current Pharmaceutical Design Peripheral and Central Glutamate Dyshomeostasis in Neurodegenerative Disorders
Current Neuropharmacology Melanocortins As Innovative Drugs for Ischemic Diseases and Neurodegenerative Disorders: Established Data and Perspectives
Current Medicinal Chemistry Gene Transfer to the Central Nervous System: Current State of the Art of the Viral Vectors
Current Genomics Using Mass Spectrometry-Based Peptidomics to understand the Brain and Disorders such as Parkinson’s Disease and Schizophrenia
Current Topics in Medicinal Chemistry