Abstract
Inflammation is characteristic of a broad spectrum of neurodegenerative diseases. These include Alzheimers (AD), Parkinsons (PD), and Huntingtons diseases, amyotrophic lateral sclerosis, all of the tauopathies, multiple sclerosis and many other less common conditions. Morphologically, the level of inflammation is determined by the concentration and degree of activation of microglial cells. Biochemically, it is judged by the presence of a spectrum of inflammatory mediators. Epidemiological evidence indicates that anti-inflammatory agents such as non-steroidal anti-inflammatory drugs (NSAIDs) have a sparing effect on AD and PD indicating that inflammation exacerbates the pathology in these diseases. NSAIDs are protective in transgenic animal models of AD, providing further evidence of the negative consequences of inflammation. Here we describe an in vitro model, which was used to study the protective effects of NSAIDs in AD. This model is based on neuronal cell killing by stimulated microglia or microglia-like cells. In this model NSAIDs show protective effects at a therapeutically relevant level, which is in the low micromolar range. There are reports suggesting that NSAIDs act independently of cyclooxygenase (COX) inhibition, but only at higher doses. Classical NSAIDs are still the most logical choice for agents that will slow the progression or delay the onset of AD and other neurodegenerative diseases despite failures of naproxen, celecoxib and rofecoxib in AD clinical trials. Several other classes of anti-inflammatory drugs have been identified as potentially beneficial in this and similar assay systems. Therefore combination therapy with other anti-inflammatory agents that work through different mechanisms of action might prove to be a superior therapeutic strategy.
Keywords: alzheimers disease, cyclooxygenases, inflammation, microglia, multiple sclerosis, neuroprotection, neurotoxicity, parkinsons disease
Current Alzheimer Research
Title: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Other Anti- Inflammatory Agents in the Treatment of Neurodegenerative Disease
Volume: 2 Issue: 3
Author(s): Andis Klegeris and Patrick L. McGeer
Affiliation:
Keywords: alzheimers disease, cyclooxygenases, inflammation, microglia, multiple sclerosis, neuroprotection, neurotoxicity, parkinsons disease
Abstract: Inflammation is characteristic of a broad spectrum of neurodegenerative diseases. These include Alzheimers (AD), Parkinsons (PD), and Huntingtons diseases, amyotrophic lateral sclerosis, all of the tauopathies, multiple sclerosis and many other less common conditions. Morphologically, the level of inflammation is determined by the concentration and degree of activation of microglial cells. Biochemically, it is judged by the presence of a spectrum of inflammatory mediators. Epidemiological evidence indicates that anti-inflammatory agents such as non-steroidal anti-inflammatory drugs (NSAIDs) have a sparing effect on AD and PD indicating that inflammation exacerbates the pathology in these diseases. NSAIDs are protective in transgenic animal models of AD, providing further evidence of the negative consequences of inflammation. Here we describe an in vitro model, which was used to study the protective effects of NSAIDs in AD. This model is based on neuronal cell killing by stimulated microglia or microglia-like cells. In this model NSAIDs show protective effects at a therapeutically relevant level, which is in the low micromolar range. There are reports suggesting that NSAIDs act independently of cyclooxygenase (COX) inhibition, but only at higher doses. Classical NSAIDs are still the most logical choice for agents that will slow the progression or delay the onset of AD and other neurodegenerative diseases despite failures of naproxen, celecoxib and rofecoxib in AD clinical trials. Several other classes of anti-inflammatory drugs have been identified as potentially beneficial in this and similar assay systems. Therefore combination therapy with other anti-inflammatory agents that work through different mechanisms of action might prove to be a superior therapeutic strategy.
Export Options
About this article
Cite this article as:
Klegeris Andis and McGeer L. Patrick, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Other Anti- Inflammatory Agents in the Treatment of Neurodegenerative Disease, Current Alzheimer Research 2005; 2 (3) . https://dx.doi.org/10.2174/1567205054367883
DOI https://dx.doi.org/10.2174/1567205054367883 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
Erythropoietin Signaling and Neuroprotection
Current Signal Transduction Therapy A Combination of Two Antioxidants (An SOD Mimic and Ascorbate) Produces a Pro-Oxidative Effect Forcing Escherichia coli to Adapt Via Induction of oxyR Regulon
Anti-Cancer Agents in Medicinal Chemistry Mitochondria: A Promising Target for Anticancer Alkaloids
Current Topics in Medicinal Chemistry Catechol-O-methyltransferase, Cognition and Alzheimer's Disease
Current Alzheimer Research Immunophilin Dysfunction and Neuropathology
Current Medicinal Chemistry Meet Our Editorial Board Member
Current Alzheimer Research Glycogen Synthase Kinase-3: A Potential Target for Drug Discovery in the Treatment of Neurodegenerative Disorders
Current Enzyme Inhibition Flavonoids in Neurodegeneration: Limitations and Strategies to Cross CNS Barriers
Current Medicinal Chemistry Magnetic Resonance-Based Metabolomics for Understanding Neurological Disorders: Current Status and Statistical Considerations
Current Metabolomics Basic Approaches in Therapy of Multiple Sclerosis (MS) and Related Diseases: Current Achievement and Prospective
Central Nervous System Agents in Medicinal Chemistry Prediction of Disease-Related Genes Based on Hybrid Features
Current Proteomics Central Nervous System-Related
Current Bioactive Compounds Selenium and Clinical Trials: New Therapeutic Evidence for Multiple Diseases
Current Medicinal Chemistry Therapeutic Potential of Metabotropic Glutamate Receptor Modulators
Current Neuropharmacology Proteins of the Esterase Family: Patents for Some Proteins in Search of Metabolic Functions
Recent Patents on Biomarkers Mevalonate Cascade and Neurodevelopmental and Neurodegenerative Diseases: Future Targets for Therapeutic Application
Current Molecular Pharmacology Mesenchymal Stem Cells in the Treatment of Amyotrophic Lateral Sclerosis
Current Stem Cell Research & Therapy Optimization of Lentiviral Vectors Generation for Biomedical and Clinical Research Purposes: Contemporary Trends in Technology Development and Applications
Current Gene Therapy Editorial [Hot Topic: Frontotemporal Lobar Degeneration and Related Disorders (Guest Editor: Barbara Borroni)]
Current Alzheimer Research Low Molecular Weight Compounds with Transition Metals as Free Radical Scavengers and Novel Therapeutic Agents
Cardiovascular & Hematological Agents in Medicinal Chemistry