Abstract
Prostaglandins (PGs) are potent autocrine and paracrine oxygenated lipid molecules that contribute appreciably to physiologic and pathophysiologic responses in almost all organs, including brain. Emerging data indicate that the PGs, and more specifically PGE2, play a central role in brain diseases including ischemic injury and several neurodegenerative diseases. Given concerns over the potential toxicity from protracted use of cyclooxygenase inhibitors in the elderly, attention is now focused on blocking PGE2 signaling that is mediated by interactions with four distinct G protein-coupled receptors, EP1-4, which are differentially expressed on neuronal and glial cells throughout the central nervous system. EP1 activation has been shown to mediate Ca2+-dependent neurotoxicity in ischemic injury. EP2 activation has been shown to mediate microglial-induced paracrine neurotoxicity as well as suppress microglia internalization of aggregated neurotoxic peptides. Animal models support the potential efficacy of targeting specific EP receptor subtypes in Alzheimers disease, Parkinsons disease, amyotrophic lateral sclerosis, and ischemic stroke. However promising these preclinical studies are, they have yet to be followed by clinical trials targeting any EP receptor in neurologic diseases.
Keywords: Prostaglandins, PGE2, CNS, neurodegeneration, EP receptors
Current Medicinal Chemistry
Title: Therapeutic Targets in Prostaglandin E2 Signaling for Neurologic Disease
Volume: 15 Issue: 19
Author(s): P. J. Cimino, C. Dirk Keene, Richard M. Breyer, Kathleen S. Montine and Thomas J. Montine
Affiliation:
Keywords: Prostaglandins, PGE2, CNS, neurodegeneration, EP receptors
Abstract: Prostaglandins (PGs) are potent autocrine and paracrine oxygenated lipid molecules that contribute appreciably to physiologic and pathophysiologic responses in almost all organs, including brain. Emerging data indicate that the PGs, and more specifically PGE2, play a central role in brain diseases including ischemic injury and several neurodegenerative diseases. Given concerns over the potential toxicity from protracted use of cyclooxygenase inhibitors in the elderly, attention is now focused on blocking PGE2 signaling that is mediated by interactions with four distinct G protein-coupled receptors, EP1-4, which are differentially expressed on neuronal and glial cells throughout the central nervous system. EP1 activation has been shown to mediate Ca2+-dependent neurotoxicity in ischemic injury. EP2 activation has been shown to mediate microglial-induced paracrine neurotoxicity as well as suppress microglia internalization of aggregated neurotoxic peptides. Animal models support the potential efficacy of targeting specific EP receptor subtypes in Alzheimers disease, Parkinsons disease, amyotrophic lateral sclerosis, and ischemic stroke. However promising these preclinical studies are, they have yet to be followed by clinical trials targeting any EP receptor in neurologic diseases.
Export Options
About this article
Cite this article as:
Cimino J. P., Keene Dirk C., Breyer M. Richard, Montine S. Kathleen and Montine J. Thomas, Therapeutic Targets in Prostaglandin E2 Signaling for Neurologic Disease, Current Medicinal Chemistry 2008; 15 (19) . https://dx.doi.org/10.2174/092986708785132915
DOI https://dx.doi.org/10.2174/092986708785132915 |
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
-
Targeting Microglial Activation in Stroke Therapy: Pharmacological Tools and Gender Effects
Current Medicinal Chemistry Functional Genomics of Brain Aging and Alzheimers Disease: Focus on Selective Neuronal Vulnerability
Current Genomics Anti-inflammatory and Immune Therapy for Alzheimers Disease: Current Status and Future Directions
Current Neuropharmacology Insights on the Neuromodulatory Propensity of Selaginella (Sanjeevani) and its Potential Pharmacological Applications
CNS & Neurological Disorders - Drug Targets Pathophysiology of Transmissible Spongiform Encephalopathies
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Therapeutic Approaches for Lysosomal Storage Diseases: A Patent Update
Recent Patents on CNS Drug Discovery (Discontinued) Neurodegenerative Diseases and Flavonoids: Special Reference to Kaempferol
CNS & Neurological Disorders - Drug Targets Mesenchymal Stem/Stromal Cells: A New "Cells as Drugs" Paradigm. Efficacy and Critical Aspects in Cell Therapy
Current Pharmaceutical Design Advances of Phenoxazines: Synthesis, Reactivity and Their Medicinal Applications
Current Medicinal Chemistry Intrinsically Disordered Domains, Amyloids and Protein Liquid Phases: Evolving Concepts and Open Questions
Protein & Peptide Letters Modulation of Mitochondrial Permeability Transition in Ischemia-Reperfusion Injury of the Heart. Advantages and Limitations
Current Medicinal Chemistry Lipoic Acid, a Lead Structure for Multi-Target-Directed Drugs for Neurodegeneration
Mini-Reviews in Medicinal Chemistry Small Molecules in Stem Cell Research
Current Pharmaceutical Biotechnology Therapeutic Application of Histone Deacetylase Inhibitors for Stroke
Central Nervous System Agents in Medicinal Chemistry The Pharmacokinetics and Toxicology of Aluminum in the Brain
Current Inorganic Chemistry (Discontinued) Meet the Editorial Board:
Current Topics in Medicinal Chemistry Natural Triterpenoids and their Derivatives with Pharmacological Activity Against Neurodegenerative Disorders
Mini-Reviews in Organic Chemistry Thiopurine Biotransformation and Pharmacological Effects: Contribution of Oxidative Stress
Current Drug Metabolism Inflammation in the CNS: Understanding Various Aspects of the Pathogenesis of Alzheimer's Disease
Current Alzheimer Research Transcriptomics Study of Neurodegenerative Disease: Emphasis on Synaptic Dysfunction Mechanism in Alzheimer's Disease
CNS & Neurological Disorders - Drug Targets