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
-
New Drugs for Immune Targeting
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) The Activated Endocannabinoid System in Atherosclerosis: Driving Force or Protective Mechanism?
Current Drug Targets Viral MicroRNAs: Interfering the Interferon Signaling
Current Pharmaceutical Design Pathological Roles of Iron in Cardiovascular Disease
Current Drug Targets Is Autoimmunity a Component of Natural Immunity to HIV?
Current HIV Research Virtual Screening Strategies in Drug Discovery: A Critical Review
Current Medicinal Chemistry Autoimmune Diseases in Gastroenterology
Current Pharmaceutical Design Editorial [Hot topic: Targets of Research in the Metabolic Syndrome (Guest Editor: Lindsay Brown)]
Endocrine, Metabolic & Immune Disorders - Drug Targets Distribution Characteristics of ANA and ANCA in Patients with Hyperthyroidism
Endocrine, Metabolic & Immune Disorders - Drug Targets Giardiasis: An Overview
Recent Patents on Inflammation & Allergy Drug Discovery Crosstalk Between the Autophagy-Lysosome Pathway and the Ubiquitin-Proteasome Pathway in Retinal Pigment Epithelial Cells
Current Molecular Medicine Targeting Angiogenic Genes as a Therapeutic Approach for Hepatocellular Carcinoma
Current Gene Therapy Concentration-dependent Effects of Dietary L-Ascorbic Acid Fortification in the Brains of Healthy Mice
Central Nervous System Agents in Medicinal Chemistry The Effects of β -Glucans on Dendritic Cells and Implications for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Induced pluripotent stem cell-derived mesenchymal stem cells: A leap toward personalized therapies.
Current Stem Cell Research & Therapy Enzymes Metabolizing Aristolochic Acid and their Contribution to the Development of Aristolochic Acid Nephropathy and Urothelial Cancer
Current Drug Metabolism Elevated C-reactive Protein Levels in Women with Bipolar Disorder may be Explained by a History of Childhood Trauma, Especially Sexual Abuse, Body Mass Index and Age
CNS & Neurological Disorders - Drug Targets Virus-Associated Vasculitides
Current Immunology Reviews (Discontinued) Curcumin Loaded Ethosomal Gel for Improved Topical Delivery: Formulation, Characterization and <i>Ex-vivo</i> Studies
Pharmaceutical Nanotechnology Patent Selections
Recent Patents on Drug Delivery & Formulation