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 Psychopharmacology of Appetite: Targets for Potential Anti-Obesity Agents
Current Medicinal Chemistry - Central Nervous System Agents Topical Dermatological Drug Delivery: Quo Vadis?
Current Drug Delivery The Multiple Layers of Signaling Selectivity at Protease-Activated Receptors
Current Pharmaceutical Design Wound Healing Effect of an in Situ Forming Hydrogel Loading Curcumin-Phospholipid Complex
Current Drug Delivery HLA-G - From Fetal Tolerance to a Regulatory Molecule in Inflammatory Diseases
Current Immunology Reviews (Discontinued) Metformin - The Drug for the Treatment of Autoimmune Diseases; A New Use of a Known Anti-Diabetic Drug
Current Topics in Medicinal Chemistry Correlates of Immune Protection from Tuberculosis
Current Molecular Medicine Resident Kidney Cells and Their Involvement in Glomerulonephritis
Current Drug Targets - Inflammation & Allergy Novel Therapeutic Potential of Mitogen-Activated Protein Kinase Activated Protein Kinase 2 (MK2) in Chronic Airway Inflammatory Disorders
Current Drug Targets Tumor Growth-Promoting Properties of Macrophage Migration Inhibitory Factor
Current Pharmaceutical Design Endothelial Progenitor Cells and In-stent Restenosis
Current Stem Cell Research & Therapy Non-Viral Nucleic Acid Delivery: Key Challenges and Future Directions
Current Drug Delivery Gene Therapy: How to Target the Kidney. Promises and Pitfalls
Current Gene Therapy Recent Advances in Epitope Design for Immunotherapy of Cancer
Recent Patents on Anti-Cancer Drug Discovery Therapeutic Exploitation of Viral Interference
Infectious Disorders - Drug Targets Negative Regulation of TCR Signaling in Immunological Tolerance: Taming Good and Evil
Current Immunology Reviews (Discontinued) Challenges and Controversies in Autoantibodies Associated with Systemic Rheumatic Diseases
Current Rheumatology Reviews Recent Advances in Physical Approaches for Transdermal Penetration Enhancement
Current Drug Therapy Selenium Compounds and Apoptotic Modulation: A New Perspective in Cancer Therapy
Mini-Reviews in Medicinal Chemistry Antioxidant Therapy for the Treatment of Oxidative Stress Associated to Cancer and Cancer- Related Anorexia/Cachexia
Current Nutrition & Food Science