Abstract
Corticosteroids are the mainstay treatment for most severe inflammatory disorders. Due to the considerable toxicity associated with their long-term use, there is a great need for alternative treatments. Recently, two closely related neuropeptides with potent neuromodulatory activities, vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase activating peptide (PACAP) have emerged as candidate molecules for the treatment of such pathologies. These peptides act primarily on three high affinity receptor subtypes expressed on multiple immune cell types, and orchestrate a cytokine response that is primarily anti-inflammatory. In this regard, systemic treatment with these peptides has been shown to greatly reduce the clinical symptoms and alter the pathogenic and cytokine profiles in animal models of rheumatoid arthritis, Crohns disease, septic shock, and multiple sclerosis. Likewise, VIP and PACAP receptor knockout and overexpressing mice show altered immune responses in different models. We review here data demonstrating the potential effectiveness of these peptides in immune disorders, discuss receptor pharmacology and signaling pathways, describe the development of receptor specific agonists and antagonists, and discuss pharmaceutical considerations relevant to the specific delivery of analogs to the appropriate targets.
Keywords: pituitary adenylyl cyclase activating peptide (PACAP), Septic shock, Asthma, CIA mice, myelinization, inflammatory diseases
Current Topics in Medicinal Chemistry
Title: Neuropeptide Mimetics and Antagonists in the Treatment of Inflammatory Disease: Focus on VIP and PACAP
Volume: 6 Issue: 2
Author(s): Catalina Abad, Rosa P. Gomariz and James A. Waschek
Affiliation:
Keywords: pituitary adenylyl cyclase activating peptide (PACAP), Septic shock, Asthma, CIA mice, myelinization, inflammatory diseases
Abstract: Corticosteroids are the mainstay treatment for most severe inflammatory disorders. Due to the considerable toxicity associated with their long-term use, there is a great need for alternative treatments. Recently, two closely related neuropeptides with potent neuromodulatory activities, vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase activating peptide (PACAP) have emerged as candidate molecules for the treatment of such pathologies. These peptides act primarily on three high affinity receptor subtypes expressed on multiple immune cell types, and orchestrate a cytokine response that is primarily anti-inflammatory. In this regard, systemic treatment with these peptides has been shown to greatly reduce the clinical symptoms and alter the pathogenic and cytokine profiles in animal models of rheumatoid arthritis, Crohns disease, septic shock, and multiple sclerosis. Likewise, VIP and PACAP receptor knockout and overexpressing mice show altered immune responses in different models. We review here data demonstrating the potential effectiveness of these peptides in immune disorders, discuss receptor pharmacology and signaling pathways, describe the development of receptor specific agonists and antagonists, and discuss pharmaceutical considerations relevant to the specific delivery of analogs to the appropriate targets.
Export Options
About this article
Cite this article as:
Abad Catalina, Gomariz P. Rosa and Waschek A. James, Neuropeptide Mimetics and Antagonists in the Treatment of Inflammatory Disease: Focus on VIP and PACAP, Current Topics in Medicinal Chemistry 2006; 6 (2) . https://dx.doi.org/10.2174/156802606775270288
DOI https://dx.doi.org/10.2174/156802606775270288 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Molecular Hydrogen: New Antioxidant and Anti-inflammatory Therapy for Rheumatoid Arthritis and Related Diseases
Current Pharmaceutical Design Synthesis of Novel Benzoquinones with Anti-Inflammatory Activity
Letters in Drug Design & Discovery CD47 Functionalization of Nanoparticles as a Poly(ethylene glycol) Alternative: A Novel Approach to Improve Drug Delivery
Current Drug Targets Nanoparticles Based on Plasma Proteins for Drug Delivery Applications
Current Pharmaceutical Design Evidence that Pregnancy Specific Glycoproteins Regulate T-Cell Function and Inflammatory Autoimmune Disease During Pregnancy
Current Drug Targets - Inflammation & Allergy Circumventing Immune Tolerance Through Epigenetic Modification
Current Pharmaceutical Design Geriatric Depression - Review for Primary Care
Current Psychiatry Reviews Orchestrating HIV Neutralization by Secondary Immune Response- Mediated Induction of RF Antibodies
Current Immunology Reviews (Discontinued) Formation Mechanism of Insulin Fibrils and Structural Aspects of the Insulin Fibrillation Process
Current Protein & Peptide Science Modular Nanotransporters for Targeted Intracellular Delivery of Drugs: Folate Receptors as Potential Targets
Current Pharmaceutical Design New Approaches to the Modulation of the Cyclooxygenase-2 and 5-Lipoxygenase Pathways
Current Topics in Medicinal Chemistry New Pharmacological Approaches Using Polyphenols on the Physiopathology of Neuropathic Pain
Current Drug Targets Serum Procalcitonin Levels in Febrile Patients with Systemic Autoimmune Diseases
Current Rheumatology Reviews Protein Arrays: Recent Achievements and their Application to Study the Human Proteome
Current Proteomics Novel Genetic and Peptide-Based Strategies Targeting the Bcl-2 Family, an Update
Recent Patents on DNA & Gene Sequences Interactions Between Airway Epithelial Cells and Dendritic Cells: Implications for the Regulation of Airway Inflammation
Current Drug Targets Platelets in Alzheimer’s Disease-Associated Cellular Senescence and Inflammation
Current Pharmaceutical Design Histidine Hydrogen Bonding in MHC at pH 5 and pH 7 Modeled by Molecular Docking and Molecular Dynamics Simulations
Current Computer-Aided Drug Design Thalidomide Chemotherapy-Induced Peripheral Neuropathy: Actual Status and New Perspectives with Thalidomide Analogues Derivatives
Mini-Reviews in Medicinal Chemistry Effects of Chrisotherapeutic Gold Compounds on Prostaglandin E2 Production
Current Drug Targets - Inflammation & Allergy