Abstract
Alzheimers disease (AD) is accompanied by an activation of the innate immune system, and many epidemiological studies have shown reduced risk for dementia or AD associated with chronic consumption of non-steroidal anti-inflammatory drugs (NSAIDS). These observations led to animal model studies to test the hypothesis that NSAIDs can be disease-modifying for some aspects of AD pathogenesis. NSAIDS cannot only suppress inflammatory targets, which could contribute to neuroprotection, they also slow amyloid deposition by mechanisms that remain unclear. Several large clinical trials with NSAID therapies with AD subjects have failed, and cyclooxygenase-2 does not appear to be a useful target for disease modifying therapy. However, there may be apolipoprotein E E4 pharmacogenomic effects and a real but delayed positive signal in a large primary prevention trial with naproxen. This encourages researchers to re-address possible mechanisms for a stage-dependent NSAID efficacy, the subject of this review.
Keywords: Alzheimer's disease, cyclooxygenases, non-steroidal anti-inflammatory drugs, docosahexaenoic acid, curcumin
CNS & Neurological Disorders - Drug Targets
Title: Mechanisms of Action of Non-Steroidal Anti-Inflammatory Drugs for the Prevention of Alzheimers Disease
Volume: 9 Issue: 2
Author(s): Greg M. Cole and Sally A. Frautschy
Affiliation:
Keywords: Alzheimer's disease, cyclooxygenases, non-steroidal anti-inflammatory drugs, docosahexaenoic acid, curcumin
Abstract: Alzheimers disease (AD) is accompanied by an activation of the innate immune system, and many epidemiological studies have shown reduced risk for dementia or AD associated with chronic consumption of non-steroidal anti-inflammatory drugs (NSAIDS). These observations led to animal model studies to test the hypothesis that NSAIDs can be disease-modifying for some aspects of AD pathogenesis. NSAIDS cannot only suppress inflammatory targets, which could contribute to neuroprotection, they also slow amyloid deposition by mechanisms that remain unclear. Several large clinical trials with NSAID therapies with AD subjects have failed, and cyclooxygenase-2 does not appear to be a useful target for disease modifying therapy. However, there may be apolipoprotein E E4 pharmacogenomic effects and a real but delayed positive signal in a large primary prevention trial with naproxen. This encourages researchers to re-address possible mechanisms for a stage-dependent NSAID efficacy, the subject of this review.
Export Options
About this article
Cite this article as:
Cole Greg M. and Frautschy Sally A., Mechanisms of Action of Non-Steroidal Anti-Inflammatory Drugs for the Prevention of Alzheimers Disease, CNS & Neurological Disorders - Drug Targets 2010; 9 (2) . https://dx.doi.org/10.2174/187152710791011991
DOI https://dx.doi.org/10.2174/187152710791011991 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
Related Articles
-
Safety of Systemic Biologic Agents in the Treatment of Non-malignant Skin Disorders
Current Drug Safety Pertussis Toxin (PTX) and its Non-Toxic Derivatives as Vaccine Adjuvant and Microbicide
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Synthesis, Characterization and Potential Applications of Multifunctional PEO-PPOPEO- Magnetic Drug Delivery System
Current Medicinal Chemistry Natural Compounds Used as Therapies Targeting to Amyotrophic Lateral Sclerosis
Current Pharmaceutical Biotechnology The Therapeutic Potential of Melatonin in Neurological Disorders
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Genetic Studies of Type 2 Diabetes in South Asians: A Systematic Overview
Current Diabetes Reviews Combination Treatment in Alzheimers Disease: Results of a Randomized, Controlled Trial with Cerebrolysin and Donepezil
Current Alzheimer Research Neuroprotective Effects of Citrus Fruit-Derived Flavonoids, Nobiletin and Tangeretin in Alzheimer's and Parkinson's Disease
CNS & Neurological Disorders - Drug Targets Oxidative Stress and Antioxidants in Neurological Diseases: Is There Still Hope?
Current Drug Targets Assessing Glutamatergic Function and Dysfunction in Peripheral Tissues
Current Medicinal Chemistry Sirtuins: Common Targets in Aging and in Neurodegeneration
Current Drug Targets “Nutritional Psychiatry: Evidence of the Role of Foods in Mental Health” Part 1
Current Pharmaceutical Biotechnology Natural Products Combating Neurodegeneration: Parkinson’s Disease
Current Drug Metabolism Psychopharmacological Treatment in Pathological Gambling: A Critical Review
Current Pharmaceutical Design DNA Double Strand Breaks: A Common Theme in Neurodegenerative Diseases
Current Alzheimer Research Screening for Inhibitors of Tau Protein Aggregation into Alzheimer Paired Helical Filaments: A Ligand Based Approach Results in Successful Scaffold Hopping
Current Alzheimer Research Heparin - a Key Drug in the Treatment of the Circulatory Degenerative Diseases: Controlling its Action with Polymers
Current Pharmaceutical Design Joint Effect of ABCA7 rs4147929 and Body Mass Index on Progression from Mild Cognitive Impairment to Alzheimer’s Disease: The Shanghai Aging Study
Current Alzheimer Research Therapeutic Potential of N-Acetylcysteine for Wound Healing, Acute Bronchiolitis, and Congenital Heart Defects
Current Drug Metabolism Blocking Striatal Adenosine A2A Receptors: A New Strategy for Basal Ganglia Disorders
Recent Patents on CNS Drug Discovery (Discontinued)