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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Oxidant/Antioxidant Imbalance and the Risk of Alzheimer's Disease
Current Alzheimer Research Altering the Tropism of Lentiviral Vectors through Pseudotyping
Current Gene Therapy The Role of Minocycline in Ischemia-Reperfusion Injury: A Comprehensive Review of an Old Drug with New Implications
Recent Patents on Cardiovascular Drug Discovery Genistein: A Phytoestrogen with Multifaceted Therapeutic Properties
Mini-Reviews in Medicinal Chemistry Minocycline Repurposing in Critical Illness: Focus on Stroke
Current Topics in Medicinal Chemistry Drugs of Abuse in Pregnancy, Poor Neonatal Development, and Future Neurodegeneration. Is Oxidative Stress the Culprit?
Current Pharmaceutical Design Blood-Brain Barrier P-Glycoprotein Function in Neurodegenerative Disease
Current Pharmaceutical Design Mitochondria-Targeted Antioxidant Peptides
Current Pharmaceutical Design A Direct Interaction Between Mitochondrial Proteins and Amyloid-β Peptide and its Significance for the Progression and Treatment of Alzheimer’s Disease
Current Medicinal Chemistry Synthetic Methods for the Preparation of Triazepandiones and Review of their Applications
Current Organic Chemistry Disentangling the Role of the Tau Gene Locus in Sporadic Tauopathies
Current Alzheimer Research The Role of the Oxysterol/EBI2 Pathway in the Immune and Central Nervous Systems
Current Drug Targets Melatonin and Melatonergic Influence on Neuronal Transcription Factors: Implications for the Development of Novel Therapies for Neurodegenerative Disorders
Current Neuropharmacology The Importance of NAD in Multiple Sclerosis
Current Pharmaceutical Design Role of Methylene Blue in Trauma Neuroprotection and Neuropsychiatric Diseases
CNS & Neurological Disorders - Drug Targets Targeting Neurotrophic/Growth Factor Expression and Signaling for Antidepressant Drug Development
CNS & Neurological Disorders - Drug Targets Control and Role of Plateau Potential Properties in the Spinal Cord
Current Pharmaceutical Design State of the Art Clinical Efficacy and Safety Evaluation of N-Acetylcarnosine Dipeptide Ophthalmic Prodrug. Principles for the Delivery, Self-Bioactivation, Molecular Targets and Interaction with a Highly Evolved Histidyl-Hydrazide Structure in the Treatment and Therapeutic Management of a Group of Sight-Threatening Eye Diseases
Current Clinical Pharmacology Editorial (Thematic Issue: Microglia - A Therapeutic Target in Neurological Diseases and Disorders)
CNS & Neurological Disorders - Drug Targets Nanoparticle-Based Gene Therapy Intervention for Stroke Treatment: A Systematic Review
Current Gene Therapy