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
-
Alcohol Drinking, Apolipoprotein Polymorphisms and the Risk of Cardiovascular Diseases
Current Neurovascular Research Two Nitrogen-containing Ligands as Inhibitors of Metal-Induced Amyloid β-Peptide Aggregation
CNS & Neurological Disorders - Drug Targets Alzheimer’s Disease, Astrocytes and Kynurenines
Current Alzheimer Research Frontier View on Nanotechnological Strategies for Neuro-therapy
Current Drug Metabolism The Potential of Serratiopetidase and Lumbrokinase for the Degradation of Prion Peptide 106-126 - an <i>In Vitro</i> and <i>In Silico</i> Perspective
CNS & Neurological Disorders - Drug Targets Functional Annotation of Genes Overlapping Copy Number Variants in Autistic Patients: Focus on Axon Pathfinding
Current Genomics Reduced Alzheimer’s Disease Pathology by St. John’s Wort Treatment is Independent of Hyperforin and Facilitated by ABCC1 and Microglia Activation in Mice
Current Alzheimer Research Structurally Related Edaravone Analogues: Synthesis, Antiradical, Antioxidant, and Copper-Chelating Properties
CNS & Neurological Disorders - Drug Targets Potential Therapeutic Targets for Neurodegenerative Diseases: Lessons Learned from Calorie Restriction
Current Drug Targets Hydroximic Acid Derivatives: Pleiotropic Hsp Co-Inducers Restoring Homeostasis and Robustness
Current Pharmaceutical Design Plant Polyphenols and Tumors: From Mechanisms to Therapies, Prevention, and Protection Against Toxicity of Anti-Cancer Treatments
Current Medicinal Chemistry Nutraceuticals for Promoting Longevity
Current Nutraceuticals Isolated Mitochondrial Complex I Deficiency: Explorative Data Analysis of Patient Cell Parameters
Current Pharmaceutical Design Insulin Resistance in Alzheimer Disease: p53 and MicroRNAs as Important Players
Current Topics in Medicinal Chemistry Mitochondria: Prospective Targets for Neuroprotection in Parkinson's Disease
Current Pharmaceutical Design Vascular Risk Factors and Neurodegeneration in Ageing Related Dementias: Alzheimer’s Disease and Vascular Dementia
Current Alzheimer Research Reconceptualizing Adult Neurogenesis: Role for Sphingosine-1-Phosphate and Fibroblast Growth Factor-1 in Co-Ordinating Astrocyte-Neuronal Precursor Interactions
CNS & Neurological Disorders - Drug Targets Past and Recent Progress of Molecular Imaging Probes for β-Amyloid Plaques in the Brain
Current Medicinal Chemistry Neurochemistry Changes Associated with Mutations in Familial Parkinsons Disease
Current Medicinal Chemistry Dissecting the Mechanisms of Thrombogenesis and Atherosclerosis for Neurodegenerative Disorders
Current Neurovascular Research