Abstract
In the human brain several cell types are capable of initiating and amplifying a brain specific inflammatory response involving the synthesis of cytokines, prostaglandins and oxygen free radicals. In Alzheimers disease (AD), signs of an inflammatory activation of microglia and astroglia are present inside and outside amyloid deposits. Cell culture and animal models suggest an interactive relationship between inflammatory activation, reduced neuronal functioning and deposition of amyloid. The activation of inflammation-associated enzymes such as p38 mitogen-activated protein kinase (p38 MAPK) and cycloxygenase-2 (COX-2) is not restricted to glial cells but also found in neurons and may contribute to intraneuronal damage. Epidemiological studies have shown a reduced risk of AD among users of anti-inflammatory drugs. Therefore, anti-inflammatory drugs have become the focus of several new treatment strategies. Small clinical trials with non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and diclofenac showed a trend for a disease modifying effect, while clinical trials with steroids did not show a beneficial effect. NSAIDs may not only act on COX-2 but also inhibit COX-1 activity or activate peroxisome proliferator-activated receptor gamma (PPARγ. Among promising new strategies to reduce the inflammatory activation in the CNS interfering with intracellular pro-inflammatory pathways has been shown to be effective in various cell culture and animal models. Inhibitors of p38MAPK and PPARγ agonists may be suitable agents to suppress inflammatory activation in AD.
Keywords: Alzheimers Disease, Microglia, Astroglia, p38 mitogen-activated protein kinase (p38 MAPK), cycloxygenase-2 (COX-2), non-steroidal anti-inflammatory drugs (NSAIDs), peroxisome proliferator-activated receptor, anti-inflammatory drugs
Current Medicinal Chemistry
Title: Pathways of Inflammatory Activation in Alzheimers Disease: Potential Targets for Disease Modifying Drugs
Volume: 9 Issue: 1
Author(s): M. Hull, K. Lieb and B. L. Fiebich
Affiliation:
Keywords: Alzheimers Disease, Microglia, Astroglia, p38 mitogen-activated protein kinase (p38 MAPK), cycloxygenase-2 (COX-2), non-steroidal anti-inflammatory drugs (NSAIDs), peroxisome proliferator-activated receptor, anti-inflammatory drugs
Abstract: In the human brain several cell types are capable of initiating and amplifying a brain specific inflammatory response involving the synthesis of cytokines, prostaglandins and oxygen free radicals. In Alzheimers disease (AD), signs of an inflammatory activation of microglia and astroglia are present inside and outside amyloid deposits. Cell culture and animal models suggest an interactive relationship between inflammatory activation, reduced neuronal functioning and deposition of amyloid. The activation of inflammation-associated enzymes such as p38 mitogen-activated protein kinase (p38 MAPK) and cycloxygenase-2 (COX-2) is not restricted to glial cells but also found in neurons and may contribute to intraneuronal damage. Epidemiological studies have shown a reduced risk of AD among users of anti-inflammatory drugs. Therefore, anti-inflammatory drugs have become the focus of several new treatment strategies. Small clinical trials with non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and diclofenac showed a trend for a disease modifying effect, while clinical trials with steroids did not show a beneficial effect. NSAIDs may not only act on COX-2 but also inhibit COX-1 activity or activate peroxisome proliferator-activated receptor gamma (PPARγ. Among promising new strategies to reduce the inflammatory activation in the CNS interfering with intracellular pro-inflammatory pathways has been shown to be effective in various cell culture and animal models. Inhibitors of p38MAPK and PPARγ agonists may be suitable agents to suppress inflammatory activation in AD.
Export Options
About this article
Cite this article as:
Hull M., Lieb K. and Fiebich L. B., Pathways of Inflammatory Activation in Alzheimers Disease: Potential Targets for Disease Modifying Drugs, Current Medicinal Chemistry 2002; 9 (1) . https://dx.doi.org/10.2174/0929867023371292
DOI https://dx.doi.org/10.2174/0929867023371292 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
The Characteristic of Histopathology in Spondyloarthropathy
Current Rheumatology Reviews Enzyme Mediated Baeyer-Villiger Oxidations
Current Organic Chemistry From Body Art to Anticancer Activities: Perspectives on Medicinal Properties of Henna
Current Drug Targets Graft Versus Host Disease
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents The Renin-Angiotensin System and the Neurodegenerative Diseases: A Brief Review
Protein & Peptide Letters Beta-Blockers: Current State of Knowledge and Perspectives
Mini-Reviews in Medicinal Chemistry Nrf2 and NF-κB Modulation by Sulforaphane Counteracts Multiple Manifestations of Diabetic Neuropathy in Rats and High Glucose-Induced Changes
Current Neurovascular Research The Association of Microglial Activation and Amyloid Reduction in APP+PS1 Transgenic Mice
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Synthesis and in vitro Evaluation of the Anticancer Potential of New Aminoalkanol Derivatives of Xanthone
Anti-Cancer Agents in Medicinal Chemistry Non Peptidic Urotensin II Antagonists: Perspectives for a New Class of Drugs
Cardiovascular & Hematological Agents in Medicinal Chemistry The Role of Aryl Hydrocarbon Receptor-Regulated Cytochrome P450 Enzymes in Glioma
Current Pharmaceutical Design Synthesis of Asymmetric 1-Thiocarbamoyl Pyrazoles as Potent Anti- Colon Cancer, Antioxidant and Anti-Inflammatory Agent
Anti-Cancer Agents in Medicinal Chemistry Inhibition of Sphingomyelin Hydrolysis: Targeting the Lipid Mediator Ceramide as a Key Regulator of Cellular Fate
Current Medicinal Chemistry Biologic Therapies in Primary Sjögren's Syndrome
Current Pharmaceutical Biotechnology A Comprehensive Review on the Biological and Pharmacological Activities of Rhodanine Based Compounds for Research and Development of Drugs
Mini-Reviews in Medicinal Chemistry Diagnosis and Treatment of Pulmonary Fungal Infections in Critically Ill Patients
Current Respiratory Medicine Reviews Targeting Invasion Induction as a Therapeutic Strategy for the Treatment of Cancer
Current Cancer Drug Targets Kinetics and Docking Studies of a COX-2 Inhibitor Isolated from Terminalia bellerica Fruits
Protein & Peptide Letters Activation of Integrin β1 Mediates the Increased Malignant Potential of Ovarian Cancer Cells Exerted by Inflammatory Cytokines
Anti-Cancer Agents in Medicinal Chemistry Current Progress in the Development of HIV Vaccines
Current Pharmaceutical Design