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
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
-
Advanced Glycation End Products: Association with the Pathogenesis of Diseases and the Current Therapeutic Advances
Current Clinical Pharmacology Capillary Electrophoresis Interfaced with a Mass Spectrometer (CE-MS): Technical Considerations and Applicability for Biomarker Studies in Animals
Current Protein & Peptide Science Targeting CNS Transporters for Treatment of Neurodegenerative Diseases
Current Pharmaceutical Design Understanding Abnormal c-JNK/p38MAPK Signaling in Amyotrophic Lateral Sclerosis: Potential Drug Targets and Influences on Neurological Disorders
CNS & Neurological Disorders - Drug Targets Multi-Target-Directed Ligands and other Therapeutic Strategies in the Search of a Real Solution for Alzheimer’s Disease
Current Neuropharmacology Can Transcriptomics Cut the Gordian Knot of Amyotrophic Lateral Sclerosis?
Current Genomics The Role of Nicotinamide Phosphoribosyltransferase in Cerebral Ischemia
Current Topics in Medicinal Chemistry Tandem Repeat Peptide Strategy for the Design of Neurotrophic Factor Mimetics
CNS & Neurological Disorders - Drug Targets Withania somnifera Phytochemicals Confer Neuroprotection by Inhibition of the Catalytic Domain of Human Matrix Metalloproteinase-9
Letters in Drug Design & Discovery Glutamatergic Neurotransmission As Molecular Target of New Anticonvulsants
Current Topics in Medicinal Chemistry Exploring Multiple Sclerosis (MS) and Amyotrophic Lateral Scler osis (ALS) as Neurodegenerative Diseases and their Treatments: A Review Study
Current Topics in Medicinal Chemistry Mitochondrial Generation of Reactive Oxygen Species and its Role in Aerobic Life
Current Medicinal Chemistry Targeting Glutamatergic Signaling for the Development of Novel Therapeutics for Mood Disorders
Current Pharmaceutical Design Stem Cell-Derived Oligodendroglial Cells for Therapy in Neurological Diseases
Current Stem Cell Research & Therapy The Application of Proteomics in Neurology
Current Proteomics Cyclin-Dependent Kinase Inhibitors: Cancer Killers to Neuronal Guardians
Current Medicinal Chemistry Metallothionein is a Potential Therapeutic Strategy for Amyotrophic Lateral Sclerosis
Current Pharmaceutical Design Machine Learning Approaches in Parkinson’s Disease
Current Medicinal Chemistry Therapeutic Approaches Targeting Pathological Tau Aggregates
Current Pharmaceutical Design Anti-Inflammatory Activity of Tetracyclines: Applications to Human Disease
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry