Abstract
Secretory phospholipases A2 (sPLA2s) are a subfamily of lipolytic enzymes which hydrolyze the acyl bond at the sn-2 position of glycerophospholipids to produce free fatty acids and lysophospholipids. These products are precursors of bioactive eicosanoids and platelet-activating factor (PAF). The hydrolysis of membrane phospholipids by PLA2 is a rate-limiting step for generation of eicosanoids and PAF. To date, more than 10 isozymes of sPLA2 have been found in the mammalian central nervous system (CNS). Under physiological conditions, sPLA2s are involved in diverse cellular responses, including host defense, phospholipid digestion and metabolism. However, under pathological situations, increased sPLA2 activity and excessive production of free fatty acids and their metabolites may lead to inflammation, loss of membrane integrity, oxidative stress, and subsequent tissue injury. Emerging evidence suggests that sPLA2 plays a role in the secondary injury process after traumatic or ischemic injuries in the brain and spinal cord. Importantly, sPLA2 may act as a convergence molecule that mediates multiple key mechanisms involved in the secondary injury since it can be induced by multiple toxic factors such as inflammatory cytokines, free radicals, and excitatory amino acids, and its activation and metabolites can exacerbate the secondary injury. Blocking sPLA2 action may represent a novel and efficient strategy to block multiple injury pathways associated with the CNS secondary injury. This review outlines the current knowledge of sPLA2 in the CNS with emphasis placed on the possible roles of sPLA2 in mediating CNS injuries, particularly the traumatic and ischemic injuries in the brain and spinal cord.
Keywords: Phospholipases A, spinal cord injury, ischemia, excitatory amino acids, reactive oxygen species, inflammation, lipid metabolism, cytokines
CNS & Neurological Disorders - Drug Targets
Title: Role of Secretory Phospholipase A2 in CNS Inflammation: Implications in Traumatic Spinal Cord Injury
Volume: 7 Issue: 3
Author(s): W. Lee Titsworth, Nai-Kui Liu and Xiao-Ming Xu
Affiliation:
Keywords: Phospholipases A, spinal cord injury, ischemia, excitatory amino acids, reactive oxygen species, inflammation, lipid metabolism, cytokines
Abstract: Secretory phospholipases A2 (sPLA2s) are a subfamily of lipolytic enzymes which hydrolyze the acyl bond at the sn-2 position of glycerophospholipids to produce free fatty acids and lysophospholipids. These products are precursors of bioactive eicosanoids and platelet-activating factor (PAF). The hydrolysis of membrane phospholipids by PLA2 is a rate-limiting step for generation of eicosanoids and PAF. To date, more than 10 isozymes of sPLA2 have been found in the mammalian central nervous system (CNS). Under physiological conditions, sPLA2s are involved in diverse cellular responses, including host defense, phospholipid digestion and metabolism. However, under pathological situations, increased sPLA2 activity and excessive production of free fatty acids and their metabolites may lead to inflammation, loss of membrane integrity, oxidative stress, and subsequent tissue injury. Emerging evidence suggests that sPLA2 plays a role in the secondary injury process after traumatic or ischemic injuries in the brain and spinal cord. Importantly, sPLA2 may act as a convergence molecule that mediates multiple key mechanisms involved in the secondary injury since it can be induced by multiple toxic factors such as inflammatory cytokines, free radicals, and excitatory amino acids, and its activation and metabolites can exacerbate the secondary injury. Blocking sPLA2 action may represent a novel and efficient strategy to block multiple injury pathways associated with the CNS secondary injury. This review outlines the current knowledge of sPLA2 in the CNS with emphasis placed on the possible roles of sPLA2 in mediating CNS injuries, particularly the traumatic and ischemic injuries in the brain and spinal cord.
Export Options
About this article
Cite this article as:
Titsworth Lee W., Liu Nai-Kui and Xu Xiao-Ming, Role of Secretory Phospholipase A2 in CNS Inflammation: Implications in Traumatic Spinal Cord Injury, CNS & Neurological Disorders - Drug Targets 2008; 7 (3) . https://dx.doi.org/10.2174/187152708784936671
DOI https://dx.doi.org/10.2174/187152708784936671 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
Related Articles
-
The Pathophysiological Basis of Renal Nerve Ablation for the Treatment of Hypertension
Current Vascular Pharmacology Functions of MAPR (Membrane-Associated Progesterone Receptor) Family Members As Heme/Steroid-Binding Proteins
Current Protein & Peptide Science Roles and Therapeutic Potential of Metallothioneins in Neurodegenerative Diseases
Current Pharmaceutical Biotechnology REM Sleep Behavior Disorder and Narcolepsy
CNS & Neurological Disorders - Drug Targets The Decisive Role of Mutual Arrangement of Hydroxy and Methoxy Groups in (3(4)-hydroxy-4(3)-methoxyphenyl)-4,7-dimethyl-3,4,4a,5,8,8ahexahydro- 2H-chromene-4,8-diols in their Biological Activity
Letters in Drug Design & Discovery The Potential Role of Glycogen Synthase Kinase 3 Inhibitors as Amyotrophic Lateral Sclerosis Pharmacological Therapy
Current Medicinal Chemistry Targeting the Cholinergic System for Neuroprotection and/or Enhancement of Functional Recovery Following Neurotrauma
Current Pharmaceutical Design Nanotechnologies: A Strategy to Overcome Blood-Brain Barrier
Current Drug Metabolism The Effects of Physical and Psychological Stress on the Gastrointestinal Tract: Lessons from Animal Models
Current Molecular Medicine Acid-Sensing Ion Channels: A Novel Therapeutic Target for Pain and Anxiety
Current Pharmaceutical Design Tissue Engineering Scaffolds Derived from Chitosan
Current Organic Chemistry Pharmacological Modulation of the State of Awareness in Patients with Disorders of Consciousness: An Overview
Current Pharmaceutical Design Editorial (Hot Topic: Regenerative Medicine in Neurological Diseases)
Recent Patents on Regenerative Medicine Different Treatment Strategies for Pediatric Brain Tumors
Current Pediatric Reviews Mast Cells: Target and Source of Neuropeptides
Current Pharmaceutical Design Editorials (Stem Cell Tourism in the Era of Personalized Medicine: What We Know, and What We Need to Know)
Current Pharmacogenomics and Personalized Medicine Stem Cells: In Sickness and in Health
Current Stem Cell Research & Therapy CAM Use in Pediatric Oncology
Current Pediatric Reviews Alzheimer's Disease: Related Targets, Synthesis of Available Drugs, Bioactive Compounds Under Development and Promising Results Obtained from Multi-target Approaches
Current Drug Targets Editorial [Hot Topic: Regulation of Glutamate Synthesis Via Inhibition of Glutamate Carboxypeptidase II (GCPII): An Effective Method to Treat Central and Peripheral Nervous System Disorders (Guest Editors: Guido Cavaletti and Barbara Slusher)]
Current Medicinal Chemistry