Abstract
The tripeptide glycine-proline-glutamate (GPE) is the naturally cleaved N-terminal tripeptide of insulin-like growth factor-1 (IGF-1) in brain tissues by an acid protease. Although GPE does not bind to IGF-1 receptors and its mode of action is not clear, in vitro studies have demonstrated its ability to stimulate acetylcholine and dopamine release, as well as to protect neurones from diverse induced brain injures. More importantly, GPE has been shown to have potent neuroprotective effects in numerous animal models of hypoxic-ischemic brain injury and neurodegenerative diseases such as Parkinsons, Alzheimers and Huntingtons diseases. As a consequence, GPE was suggested to be a potential target for the rational design of neuroprotective agents. Unfortunately, the use of GPE as a therapeutic agent is limited because of its unfavorable biochemical and pharmacokinetic properties. This review will focus on structural modifications performed on the GPE molecule in order to obtain bioactive analogues with increased pharmacokinetic profile useful for the treatment of central nervous system (CNS) injures and neurodegenerative disorders.
Keywords: Glycine-proline-glutamate, GPE analogues, macrocyclic GPE analogues, structure-activity relationships, neuroprotective agents, neurodegenerative disease, hypoxic-ischemic brain injury, Huntington's diseases, neurodegenerative diseases, Ligand-receptor interactions, amino-terminal glycine, carboxy-teminal glutamate, postoperative period, proline-analogues
Mini-Reviews in Medicinal Chemistry
Title: GPE and GPE Analogues as Promising Neuroprotective Agents
Volume: 12 Issue: 1
Author(s): I. Cacciatore, C. Cornacchia, L. Baldassarre, E. Fornasari, A. Mollica, A. Stefanucci and F. Pinnen
Affiliation:
Keywords: Glycine-proline-glutamate, GPE analogues, macrocyclic GPE analogues, structure-activity relationships, neuroprotective agents, neurodegenerative disease, hypoxic-ischemic brain injury, Huntington's diseases, neurodegenerative diseases, Ligand-receptor interactions, amino-terminal glycine, carboxy-teminal glutamate, postoperative period, proline-analogues
Abstract: The tripeptide glycine-proline-glutamate (GPE) is the naturally cleaved N-terminal tripeptide of insulin-like growth factor-1 (IGF-1) in brain tissues by an acid protease. Although GPE does not bind to IGF-1 receptors and its mode of action is not clear, in vitro studies have demonstrated its ability to stimulate acetylcholine and dopamine release, as well as to protect neurones from diverse induced brain injures. More importantly, GPE has been shown to have potent neuroprotective effects in numerous animal models of hypoxic-ischemic brain injury and neurodegenerative diseases such as Parkinsons, Alzheimers and Huntingtons diseases. As a consequence, GPE was suggested to be a potential target for the rational design of neuroprotective agents. Unfortunately, the use of GPE as a therapeutic agent is limited because of its unfavorable biochemical and pharmacokinetic properties. This review will focus on structural modifications performed on the GPE molecule in order to obtain bioactive analogues with increased pharmacokinetic profile useful for the treatment of central nervous system (CNS) injures and neurodegenerative disorders.
Export Options
About this article
Cite this article as:
Cacciatore I., Cornacchia C., Baldassarre L., Fornasari E., Mollica A., Stefanucci A. and Pinnen F., GPE and GPE Analogues as Promising Neuroprotective Agents, Mini-Reviews in Medicinal Chemistry 2012; 12 (1) . https://dx.doi.org/10.2174/138955712798868995
DOI https://dx.doi.org/10.2174/138955712798868995 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...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
-
Mechanisms of Inhibitory and Regulatory Effects of Methylenedioxyphenyl Compounds on Cytochrome P450-Dependent Drug Oxidation
Current Drug Metabolism Molecular Imaging in the Default Mode Network
Current Molecular Imaging (Discontinued) Membrane Estrogen Receptors Acting in the Central Nervous System
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Molecular Mechanisms Underlying the Dedifferentiation Process of Isolated Hepatocytes and Their Cultures
Current Drug Metabolism Curcumin: the Yellow Molecule with Pleiotropic Biological Effects
Letters in Drug Design & Discovery Current Signal Transduction Therapy for Brain Tumors Review Article
Current Signal Transduction Therapy Evaluation of Pharmacological Treatment Strategies in Traumatic Brain Injury
Current Pharmaceutical Design Selective Modulator of Cannabinoid Receptor Type 2 Reduces Memory Impairment and Infarct Size During Cerebral Hypoperfusion and Vascular Dementia
Current Neurovascular Research Gene Therapy as a Novel Pharmaceutical Intervention for Stroke
Current Pharmaceutical Design Application of Mesenchymal Stem Cells in Melanoma: A Potential Therapeutic Strategy for Delivery of Targeted Agents
Current Medicinal Chemistry The Effect of Claudin-5 Overexpression on the Interactions of Claudin-1 and -2 and Barrier Function in Retinal Cells
Current Molecular Medicine Vasculopathy in Hyperthyroid Rats and Targets for Drug Effects
Vascular Disease Prevention (Discontinued) Candidate Susceptibility Genes in Alzheimers Disease Are at High Risk for Being Forgotten - They Dont Give Peace of Mind...
Current Drug Metabolism Opioids and Mechanical Ventilation
Current Drug Targets Adrenergic and V1-ergic Agonists/Antagonists Affecting Recovery from Brain Trauma in the Lund Project Act on Astrocytes
Current Signal Transduction Therapy Patients with Increased Non-Ceruloplasmin Copper Appear a Distinct Sub-Group of Alzheimer's Disease: A Neuroimaging Study
Current Alzheimer Research Emerging Influenza Viruses: Past and Present
Current Molecular Medicine Imidazoline Receptor Agonists for Managing Hypertension May Hold Promise for Treatment of Intracerebral Hemorrhage
Current Molecular Medicine Estrogen Receptor Signaling: Impact on Cell Functions
Current Signal Transduction Therapy Glutamatergic Neurotransmission As Molecular Target of New Anticonvulsants
Current Topics in Medicinal Chemistry