Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide that was initially isolated from hypothalamus extracts on the basis of its ability to stimulate the production of cAMP in cultured pituitary cells. Recent studies have shown that PACAP exerts potent neuroprotective effects not only in vitro but also in in vivo models of Parkinsons disease, Huntingtons disease, traumatic brain injury and stroke. The protective effects of PACAP are based on its capacity to prevent neuronal apoptosis by acting directly on neurons or indirectly through the release of neuroprotective factors by astrocytes. These biological activities are mainly mediated through activation of the PAC1 receptor which is currently considered as a potential target for the treatment of neurodegenerative diseases. However, the use of native PACAP, the endogenous ligand of PAC1, as an efficient neuroprotective drug is actually limited by its rapid degradation. Moreover, injection of PACAP to human induces peripheral side effects which are mainly mediated through VPAC1 and VPAC2 receptors. Strategies to overcome these compromising conditions include the development of metabolically stable analogs of PACAP acting as selective agonists of the PAC1 receptor. This review presents an overview of the structure- activity relationships of PACAP and summarizes the molecular and conformational requirements for activation of PAC1 receptor. The applicability of PACAP analogs as therapeutic agents for treatment of neurodegenerative diseases is also discussed.
Keywords: PACAP, PAC1 receptor, neuroprotection, neurodegenerative diseases, neurological insults, structure-activity relationships, stable analogs
Current Medicinal Chemistry
Title: Pituitary Adenylate Cyclase-Activating Polypeptide: Focus on Structure- Activity Relationships of a Neuroprotective Peptide
Volume: 16 Issue: 33
Author(s): S. Bourgault, D. Vaudry, A. Dejda, N. D. Doan, H. Vaudry and A. Fournier
Affiliation:
Keywords: PACAP, PAC1 receptor, neuroprotection, neurodegenerative diseases, neurological insults, structure-activity relationships, stable analogs
Abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide that was initially isolated from hypothalamus extracts on the basis of its ability to stimulate the production of cAMP in cultured pituitary cells. Recent studies have shown that PACAP exerts potent neuroprotective effects not only in vitro but also in in vivo models of Parkinsons disease, Huntingtons disease, traumatic brain injury and stroke. The protective effects of PACAP are based on its capacity to prevent neuronal apoptosis by acting directly on neurons or indirectly through the release of neuroprotective factors by astrocytes. These biological activities are mainly mediated through activation of the PAC1 receptor which is currently considered as a potential target for the treatment of neurodegenerative diseases. However, the use of native PACAP, the endogenous ligand of PAC1, as an efficient neuroprotective drug is actually limited by its rapid degradation. Moreover, injection of PACAP to human induces peripheral side effects which are mainly mediated through VPAC1 and VPAC2 receptors. Strategies to overcome these compromising conditions include the development of metabolically stable analogs of PACAP acting as selective agonists of the PAC1 receptor. This review presents an overview of the structure- activity relationships of PACAP and summarizes the molecular and conformational requirements for activation of PAC1 receptor. The applicability of PACAP analogs as therapeutic agents for treatment of neurodegenerative diseases is also discussed.
Export Options
About this article
Cite this article as:
Bourgault S., Vaudry D., Dejda A., Doan D. N., Vaudry H. and Fournier A., Pituitary Adenylate Cyclase-Activating Polypeptide: Focus on Structure- Activity Relationships of a Neuroprotective Peptide, Current Medicinal Chemistry 2009; 16 (33) . https://dx.doi.org/10.2174/092986709789712899
DOI https://dx.doi.org/10.2174/092986709789712899 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
The Response of the Aged Brain to Stroke: Too Much, Too Soon?
Current Neurovascular Research Nitric Oxide Control of Proliferation in Nerve Cells and in Tumor Cells of Nervous Origin
Current Pharmaceutical Design Pharmacological Manipulation of Brain Glycogenolysis as a Therapeutic Approach to Cerebral Ischemia
Mini-Reviews in Medicinal Chemistry Age Matching Animal Models to Humans - Theoretical Considerations
Current Drug Discovery Technologies Antibody Gene Therapy: Getting Closer to Clinical Application?
Current Gene Therapy In Vitro Evidence for Competitive TSPO Binding of the Imaging Biomarker Candidates Vinpocetine and Two Iodinated DAA1106 Analogues in Post Mortem Autoradiography Experiments on Whole Hemisphere Human Brain Slices
Current Radiopharmaceuticals Recent Advances and Patents for Nerve Scaffold Biomaterials and their Use for Local, Non-Viral Delivery of Growth Factors and Nucleic Acids
Recent Patents on Biomedical Engineering (Discontinued) High Mobility Group Box-1 (HMGB1): A Potential Target in Therapeutics
Current Drug Targets Reactive Oxygen Species in Pathogenesis of Atherosclerosis
Current Pharmaceutical Design The Insulin-like Growth Factor-1 Axis and its Potential as a Therapeutic Target in Central Nervous System (CNS) Disorders
Central Nervous System Agents in Medicinal Chemistry Diabetes and Complications: Cellular Signaling Pathways, Current Understanding and Targeted Therapies
Current Drug Targets Neuropathic Pain and Lung Delivery of Nanoparticulate Drugs: An Emerging Novel Therapeutic Strategy
CNS & Neurological Disorders - Drug Targets Behavioral Effects of 2,3-Dihydro- and Oxoisoaporphine Derivatives in Post Stroke-Depressive Like Behavior in Male Balb/c Mice
Current Topics in Medicinal Chemistry Radix Angelica Sinensis Promotes Synaptic Plasticity During Cognitive Recovery in Chronically Stressed Rats
Current Neurovascular Research Mesenchymal Stem Cells as Mediators of Neural Differentiation
Current Stem Cell Research & Therapy Investigational Positive Inotropic Agents for Acute Heart Failure
Cardiovascular & Hematological Disorders-Drug Targets Mesenchymal Stem Cells of Dental Origin-Their Potential for Antiinflammatory and Regenerative Actions in Brain and Gut Damage
Current Neuropharmacology Anti-Angiogenic Therapy as a Cancer Treatment Paradigm
Current Medicinal Chemistry - Anti-Cancer Agents Intrathecal Administration of Melatonin Ameliorates the Neuroinflammation- Mediated Sensory and Motor Dysfunction in A Rat Model of Compression Spinal Cord Injury
Current Molecular Pharmacology Allosteric Modulation of Nicotinic Acetylcholine Receptors: The Concept and Therapeutic Trends
Current Pharmaceutical Design