Abstract
Cyclooxygenase-2 (COX-2), a rate-limiting enzyme converting arachidonic acid to prostaglandins and a key player in neuroinflammation, has been implicated in the pathogenesis of neurodegenerative diseases such as multiple sclerosis, Parkinsons and Alzheimers diseases, and in traumatic brain injury- and ischemia-induced neuronal damage, and epileptogenesis. Accumulated information suggests that the contribution of COX-2 to neuropathology is associated with its involvement in synaptic modification. Inhibition or elevation of COX-2 has been shown to suppress or enhance excitatory glutamatergic neurotransmission and long-term potentiation (LTP). These events are mainly mediated via PGE2, the predominant reaction product of COX-2, and the PGE2 subtype 2 receptor (EP2)-protein kinase A pathway. Recent evidence shows that endogenous cannabinoids are substrates for COX-2 and can be oxygenated by COX-2 to form new classes of prostaglandins (prostaglandin glycerol esters and prostaglandin ethanolamides). These COX-2 oxidative metabolites of endocannabinoids, as novel signaling mediators, modulate synaptic transmission and plasticity and cause neurodegeneration. The actions of these COX-2 metabolites are likely mediated by mitogen-activated protein kinase (MAPK) and inositol 1,4,5-trisphosphate (IP3) signal transduction pathways. These discoveries suggest that the contributions of COX-2 to neurotransmission and brain malfunction result not only from its conversion of arachidonic acid to classic prostaglandins but also from its oxidative metabolism of endocannabinoids to novel prostaglandins. Thus, elucidation of COX-2 in synaptic signaling may provide a mechanistic basis for designing new drugs aimed at preventing, treating or alleviating neuroinflammation-associated neurological disorders.
Keywords: Inflammation, prostaglandin E2, endocannabinoids, prostaglandin glycerol esters, prostaglandin ethanolamides, synaptic plasticity
Current Pharmaceutical Design
Title: Cyclooxygenase-2 in Synaptic Signaling
Volume: 14 Issue: 14
Author(s): Hongwei Yang and Chu Chen
Affiliation:
Keywords: Inflammation, prostaglandin E2, endocannabinoids, prostaglandin glycerol esters, prostaglandin ethanolamides, synaptic plasticity
Abstract: Cyclooxygenase-2 (COX-2), a rate-limiting enzyme converting arachidonic acid to prostaglandins and a key player in neuroinflammation, has been implicated in the pathogenesis of neurodegenerative diseases such as multiple sclerosis, Parkinsons and Alzheimers diseases, and in traumatic brain injury- and ischemia-induced neuronal damage, and epileptogenesis. Accumulated information suggests that the contribution of COX-2 to neuropathology is associated with its involvement in synaptic modification. Inhibition or elevation of COX-2 has been shown to suppress or enhance excitatory glutamatergic neurotransmission and long-term potentiation (LTP). These events are mainly mediated via PGE2, the predominant reaction product of COX-2, and the PGE2 subtype 2 receptor (EP2)-protein kinase A pathway. Recent evidence shows that endogenous cannabinoids are substrates for COX-2 and can be oxygenated by COX-2 to form new classes of prostaglandins (prostaglandin glycerol esters and prostaglandin ethanolamides). These COX-2 oxidative metabolites of endocannabinoids, as novel signaling mediators, modulate synaptic transmission and plasticity and cause neurodegeneration. The actions of these COX-2 metabolites are likely mediated by mitogen-activated protein kinase (MAPK) and inositol 1,4,5-trisphosphate (IP3) signal transduction pathways. These discoveries suggest that the contributions of COX-2 to neurotransmission and brain malfunction result not only from its conversion of arachidonic acid to classic prostaglandins but also from its oxidative metabolism of endocannabinoids to novel prostaglandins. Thus, elucidation of COX-2 in synaptic signaling may provide a mechanistic basis for designing new drugs aimed at preventing, treating or alleviating neuroinflammation-associated neurological disorders.
Export Options
About this article
Cite this article as:
Yang Hongwei and Chen Chu, Cyclooxygenase-2 in Synaptic Signaling, Current Pharmaceutical Design 2008; 14 (14) . https://dx.doi.org/10.2174/138161208784480144
DOI https://dx.doi.org/10.2174/138161208784480144 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Progress and Promise of Nur77-based Therapeutics for Central Nervous System Disorders
Current Neuropharmacology Preterm Birth and the Risk of Neurodevelopmental Disorders - Is There a Role for Epigenetic Dysregulation?
Current Genomics Deletion of Endoplasmic Reticulum Stress-Induced CHOP Protects Microvasculature Post-Spinal Cord Injury
Current Neurovascular Research Role of α- and β-adrenergic Mechanisms in the Pathogenesis of Pulmonary Injuries Characterized by Edema, Inflammation and Fibrosis
Cardiovascular & Hematological Disorders-Drug Targets A Review of QSAR studies to Discover New Drug-like Compounds Actives Against Leishmaniasis and Trypanosomiasis
Current Topics in Medicinal Chemistry Editorial (Thematic Issue: New Therapeutic Targets in Clinical Medicine)
Current Pharmaceutical Design TNF-α Inhibition as a Treatment Strategy for Neurodegenerative Disorders: New Drug Candidates and Targets
Current Alzheimer Research Serum Endocan, Neuron-Specific Enolase and Ischemia-Modified Albumin Levels in Newborns with Partial Blood Exchange Transfusion
Combinatorial Chemistry & High Throughput Screening A Role of GABA Analogues in the Treatment of Neurological Diseases
Current Medicinal Chemistry Molecular Mechanisms Determining Opposed Functional States of Microglia
Current Neuropharmacology Cannabinoids: Occurrence and Medicinal Chemistry
Current Medicinal Chemistry COVID-19 and Autoimmune Diseases: A Systematic Review of Reported Cases
Current Rheumatology Reviews Mitochondria, Cellular Stress Resistance, Somatic Cell Depletion and Lifespan
Current Aging Science Neuroprotective Effects of Ginkgolide B Against Ischemic Stroke: A Review of Current Literature
Current Topics in Medicinal Chemistry Retraction Notice: The Benefits and Risks of Different Therapies in Preventing Postoperative Nausea and Vomiting in Patients Undergoing Thyroid Surgery
Current Drug Safety FKBP Ligands as Novel Therapeutics for Neurological Disorders
Mini-Reviews in Medicinal Chemistry Clinical Pharmacology of Non-Steroidal Anti-Inflammatory Drugs: A Review
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Establishment of Cholinergic Neuron-like Cell Lines with Differential Vulnerability to Nitrosative Stress
Current Neurovascular Research Patent Selections:
Recent Patents on CNS Drug Discovery (Discontinued) Overview of Angiogenesis and the use of Bevacizumab in Patients with Malignant Gliomas
Current Signal Transduction Therapy