Abstract
Glutamate carboxypeptidase II (GCPII) is a membrane-bound binuclear zinc metallopeptidase with the highest expression levels found in the nervous and prostatic tissue. Throughout the nervous system, glia-bound GCPII is intimately involved in the neuronneuron and neuron-glia signaling via the hydrolysis of N-acetylaspartylglutamate (NAAG), the most abundant mammalian peptidic neurotransmitter. The inhibition of the GCPII-controlled NAAG catabolism has been shown to attenuate neurotoxicity associated with enhanced glutamate transmission and GCPII-specific inhibitors demonstrate efficacy in multiple preclinical models including traumatic brain injury, stroke, neuropathic and inflammatory pain, amyotrophic lateral sclerosis, and schizophrenia. The second major area of pharmacological interventions targeting GCPII focuses on prostate carcinoma; GCPII expression levels are highly increased in androgenindependent and metastatic disease. Consequently, the enzyme serves as a potential target for imaging and therapy. This review offers a summary of GCPII structure, physiological functions in healthy tissues, and its association with various pathologies. The review also outlines the development of GCPII-specific small-molecule compounds and their use in preclinical and clinical settings.
Keywords: Metalloprotease, prostate-specific membrane antigen, glutamate excitotoxicity, prostate cancer, N-acetylaspartylglutamate, Glutamate carboxypeptidase, hydrolysis, neurotoxicity, metastatic disease, pathologies
Current Medicinal Chemistry
Title: Glutamate Carboxypeptidase II in Diagnosis and Treatment of Neurologic Disorders and Prostate Cancer
Volume: 19 Issue: 6
Author(s): C. Barinka, C. Rojas, B. Slusher and M. Pomper
Affiliation:
Keywords: Metalloprotease, prostate-specific membrane antigen, glutamate excitotoxicity, prostate cancer, N-acetylaspartylglutamate, Glutamate carboxypeptidase, hydrolysis, neurotoxicity, metastatic disease, pathologies
Abstract: Glutamate carboxypeptidase II (GCPII) is a membrane-bound binuclear zinc metallopeptidase with the highest expression levels found in the nervous and prostatic tissue. Throughout the nervous system, glia-bound GCPII is intimately involved in the neuronneuron and neuron-glia signaling via the hydrolysis of N-acetylaspartylglutamate (NAAG), the most abundant mammalian peptidic neurotransmitter. The inhibition of the GCPII-controlled NAAG catabolism has been shown to attenuate neurotoxicity associated with enhanced glutamate transmission and GCPII-specific inhibitors demonstrate efficacy in multiple preclinical models including traumatic brain injury, stroke, neuropathic and inflammatory pain, amyotrophic lateral sclerosis, and schizophrenia. The second major area of pharmacological interventions targeting GCPII focuses on prostate carcinoma; GCPII expression levels are highly increased in androgenindependent and metastatic disease. Consequently, the enzyme serves as a potential target for imaging and therapy. This review offers a summary of GCPII structure, physiological functions in healthy tissues, and its association with various pathologies. The review also outlines the development of GCPII-specific small-molecule compounds and their use in preclinical and clinical settings.
Export Options
About this article
Cite this article as:
Barinka C., Rojas C., Slusher B. and Pomper M., Glutamate Carboxypeptidase II in Diagnosis and Treatment of Neurologic Disorders and Prostate Cancer, Current Medicinal Chemistry 2012; 19 (6) . https://dx.doi.org/10.2174/092986712799034888
DOI https://dx.doi.org/10.2174/092986712799034888 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Glycogen Metabolism and Brain Pathologies
Central Nervous System Agents in Medicinal Chemistry Short-Term Ultramicronized Palmitoylethanolamide Therapy in Patients with Myasthenia Gravis: a Pilot Study to Possible Future Implications of Treatment
CNS & Neurological Disorders - Drug Targets EDITORIAL [Hot Topic Recognition of Functional Roles of Free Radicals Guest Editor: István Bokkon]
Current Neuropharmacology Systemic Redox Biomarkers in Neurodegenerative Diseases
Current Drug Metabolism Understanding the Role of Hypoxia Inducible Factor During Neurodegeneration for New Therapeutics Opportunities
Current Neuropharmacology Gels and Jellies as a Dosage Form for Dysphagia Patients: A Review
Current Drug Therapy Immunophilin Dysfunction and Neuropathology
Current Medicinal Chemistry Double-Faced Role of Human Mesenchymal Stem Cells and their Role/Challenges in Cancer Therapy
Current Stem Cell Research & Therapy The Function of the Selective Inhibitors of Cycloxygenase 2
Mini-Reviews in Medicinal Chemistry Neurological Disorders in Medical Use of <i>Cannabis</i>: An Update
CNS & Neurological Disorders - Drug Targets Molecular Chaperone ORP150 in ER Stress–related Diseases
Current Pharmaceutical Design Palmitoylethanolamide Regulates Production of Pro-Angiogenic Mediators in a Model of β Amyloid-Induced Astrogliosis <i>In Vitro</i>
CNS & Neurological Disorders - Drug Targets Applying Knowledge of Enzyme Biochemistry to the Prediction of Functional Sites for Aiding Drug Discovery
Current Topics in Medicinal Chemistry Ketamine: New Indications for an Old Drug
Current Drug Targets Human Cognitive and Neuro-Psychiatric Bio-Markers in the Cardiac Peri-Operative Patient
Current Molecular Medicine Neuroprotective Effects of Fisetin in Alzheimer’s and Parkinson’s Diseases: From Chemistry to Medicine
Current Topics in Medicinal Chemistry Glaucoma Pathogenesis and Neurotrophins: Focus on the Molecular and Genetic Basis for Therapeutic Prospects
Current Neuropharmacology Meet Our Editorial Board Member:
Current Alzheimer Research Transgenic Mouse Models of Alzheimer Disease: Developing a Better Model as a Tool for Therapeutic Interventions
Current Pharmaceutical Design Functionalized magnetic nanoparticles for biomedical applications
Current Pharmaceutical Design