Abstract
Apoptosis is a regulated process leading to cell death, which is implicated both in normal development and in various pathologies including heart failure, stroke and neurodegenerative diseases. Caspase-3, a key enzyme of the apoptotic pathway, is considered as a major target for the treatment of abnormal cell death. Many factors that inhibit cell death have been identified, but the mechanisms involved are not always fully understood. Pituitary adenylate cylase-activating polypeptide (PACAP) has been shown to exert neuroprotective activities during development. PACAP also inhibits apoptosis in cardiomyopathy, decreases glutamate-induced retinal injury, reduces neuronal loss in case of stroke, and prevents ethanol neurotoxicity. Most of the antiapoptotic effects of PACAP are mediated through the PAC1 receptor. This receptor activates a transduction cascade of second messengers to stimulate Bcl-2 expression which inhibits cytochrome c release and blocks in turn caspase activation. PACAP also acts through the PI3K/Akt pathway and inhibits the expression of proapoptotic factors such as c-Jun or Bax. The remarkable effect of PACAP on the apoptotic cascade suggests that innovative PACAP derivatives could potentially be useful for treatment of post-traumatic lesions, chronic neurodegenerative diseases, cardiac ischemia and/or retinopathy.
Keywords: Apoptosis, Bcl-2, caspase, neuroprotection, PACAP, PAC1
Current Pharmaceutical Design
Title: Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Against Apoptosis
Volume: 17 Issue: 3
Author(s): Tommy Seaborn, Olfa Masmoudi-Kouli, Alain Fournier, Hubert Vaudry and David Vaudry
Affiliation:
Keywords: Apoptosis, Bcl-2, caspase, neuroprotection, PACAP, PAC1
Abstract: Apoptosis is a regulated process leading to cell death, which is implicated both in normal development and in various pathologies including heart failure, stroke and neurodegenerative diseases. Caspase-3, a key enzyme of the apoptotic pathway, is considered as a major target for the treatment of abnormal cell death. Many factors that inhibit cell death have been identified, but the mechanisms involved are not always fully understood. Pituitary adenylate cylase-activating polypeptide (PACAP) has been shown to exert neuroprotective activities during development. PACAP also inhibits apoptosis in cardiomyopathy, decreases glutamate-induced retinal injury, reduces neuronal loss in case of stroke, and prevents ethanol neurotoxicity. Most of the antiapoptotic effects of PACAP are mediated through the PAC1 receptor. This receptor activates a transduction cascade of second messengers to stimulate Bcl-2 expression which inhibits cytochrome c release and blocks in turn caspase activation. PACAP also acts through the PI3K/Akt pathway and inhibits the expression of proapoptotic factors such as c-Jun or Bax. The remarkable effect of PACAP on the apoptotic cascade suggests that innovative PACAP derivatives could potentially be useful for treatment of post-traumatic lesions, chronic neurodegenerative diseases, cardiac ischemia and/or retinopathy.
Export Options
About this article
Cite this article as:
Seaborn Tommy, Masmoudi-Kouli Olfa, Fournier Alain, Vaudry Hubert and Vaudry David, Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Against Apoptosis, Current Pharmaceutical Design 2011; 17 (3) . https://dx.doi.org/10.2174/138161211795049679
DOI https://dx.doi.org/10.2174/138161211795049679 |
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
-
Immune Checkpoint Inhibitor Therapy and Risk of Myocarditis: A Review of the Literature
Current Immunology Reviews (Discontinued) Platelets in Atherothrombosis - Diagnostic and Prognostic Value of Platelet Activation in Patients with Atherosclerotic Diseases
Current Vascular Pharmacology Editorial (Thematic Issue: Frontiers in Atherosclerosis, Heart Disease and Diabetes)
Cardiovascular & Hematological Disorders-Drug Targets Possibilities of Two-Dimensional Gel Electrophoresis in the Understanding of Human Disease
Current Proteomics The Role of Myocardial Collagen Network in Hypertensive Heart Disease
Current Hypertension Reviews Building Mosaics of Therapeutic Plasmid Gene Vectors
Current Gene Therapy Editorial [Hot topic: Innate Immunity Molecules S100A8/A9 Involved in Stress Response and Cancer Biology (Guest Editors: Claus Kerkhoff and Saeid Ghavami)]
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Adiponectin and Cardiovascular Disease: Mechanisms and New Therapeutic Approaches
Current Medicinal Chemistry DNA-drug Conjugates for Site-specific Delivery in Anti-cancer Therapy
Current Pharmacogenomics and Personalized Medicine In Vivo Imaging of Apoptosis in Cancer: Potentials and Drawbacks of Molecular Probes
Current Molecular Imaging (Discontinued) The Impact of Uncontrolled Hypertension on the Longitudinal Systolic Function of the Left Ventricle
Current Hypertension Reviews Therapeutic Applications of Calcium Metabolism Modulation in Heart Disease
Medicinal Chemistry Nanoceria: Synthesis and Biomedical Applications
Current Nanoscience Inflamm-ageing and senescence in gout: the tale of an old king’s disease.
Current Aging Science New Approach to Immunotherapy Against Organ-specific Autoimmune Diseases with T Cell Receptor and Chemokine Receptor DNA Vaccines
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Curcumin, Hesperidin, and Rutin Selectively Interfere with Apoptosis Signaling and Attenuate Streptozotocin-Induced Oxidative Stress- Mediated Hyperglycemia
Current Neurovascular Research The Application of NMR Spectroscopy for the Study of Heart Failure
Current Pharmaceutical Design Intestinal Dysbiosis, Gut Hyperpermeability and Bacterial Translocation: Missing Links Between Depression, Obesity and Type 2 Diabetes
Current Pharmaceutical Design Cardiovascular Diseases in Pregnancy - A Brief Overview
Current Cardiology Reviews Transient Receptor Potential Channels - Emerging Novel Drug Targets for the Treatment of Pain
Current Medicinal Chemistry