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
-
Cerebral Arachidonate Cascade in Dementia: Alzheimers Disease and Vascular Dementia
Current Neuropharmacology Treatment Avenues for Type 2 Diabetes and Current Perspectives on Adipokines
Current Diabetes Reviews Comparison of the Acute Hematopoietic Capacities of Erythropoietin and U-74389G Concerning Hematocrit Levels
Cardiovascular & Hematological Disorders-Drug Targets Pharmacological Management Options to Prevent and Reduce Ischemic Hemorrhagic Transformation
Current Drug Targets Randomized Clinical Stroke Trials in 2006
Current Vascular Pharmacology Nanoparticles: A Promising Therapeutic Approach in Atherosclerosis
Current Drug Delivery The Changing Landscape of Voltage-Gated Calcium Channels in Neurovascular Disorders and in Neurodegenerative Diseases
Current Neuropharmacology PDE7-Selective and Dual Inhibitors: Advances in Chemical and Biological Research
Current Medicinal Chemistry Pharmacological Drug Delivery Strategies for Improved Therapeutic Effects: Recent Advances
Current Pharmaceutical Design Flavonoids and the Brain: Evidences and Putative Mechanisms for a Protective Capacity
Current Neuropharmacology microRNA Biogenesis Pathway as a Therapeutic Target for Human Disease and Cancer
Current Pharmaceutical Design Anomalies of Self in First-Episode Psychosis
Current Psychiatry Reviews Curcumin and its Multi-target Function Against Pain and Inflammation: An Update of Pre-clinical Data
Current Drug Targets The Anti-Inflammatory Role of Minocycline in Alzheimer´s Disease
Current Alzheimer Research Techniques and Strategies to Analyze Neural Progenitor Cell Migration
Current Pharmaceutical Biotechnology Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis
Clinical Anti-Inflammatory & Anti-Allergy Drugs (Discontinued) FMRI and Multiple Sclerosis
Current Medical Imaging Role of Metallothionein in Inflammatory Lung Diseases
Current Respiratory Medicine Reviews Axotomy Leads to Reduced Calcium Increase and Earlier Termination of CCL2 Release in Spinal Motoneurons with Upregulated Parvalbumin Followed by Decreased Neighboring Microglial Activation
CNS & Neurological Disorders - Drug Targets TRPV1: On the Road to Pain Relief
Current Molecular Pharmacology