Abstract
Glutamate, first identified in 1866, is the primary excitatory neurotransmitter in the brain. While it is critically important in many highly regulated cortical functions such as learning and memory, glutamate can be much like the magic the Sorcerers Apprentice used in Goethes poem: when conjured under unregulated conditions glutamate can get quickly out of control and lead to deleterious consequences. Two broad types of glutamate receptors, the ionotropic and metabotropic, facilitate glutamatergic neurotransmission in the CNS and play key roles in regulating cognitive function. Excessive activation of these receptors leads to excitotoxicity, especially in brain regions that are developmentally and regionally vulnerable to this kind of injury. Dysregulation of glutamate signaling leads to neurodegeneration that plays a role in a number of neuropsychiatric diseases, prompting the development and utilization of novel strategies to balance the beneficial and deleterious potential of this important neurotransmitter. Inhibition of the enzyme glutamate carboxypeptidase II (GCPII) is one method of manipulating glutamate neurotransmission. Positive outcomes (decreased neuronal loss, improved cognition) have been demonstrated in preclinical models of ALS, stroke, and Multiple Sclerosis due to inhibition of GCPII, suggesting this method of glutamate regulation could serve as a therapeutic means for treating neurodegeneration and cognitive impairment.
Keywords: Glutamate, neurodegeneration, cognitive impairment, Glutamate Carboxypeptidase II (GCPII), NAAG peptidase, NAALADase, metabotropic glutamate receptor, ionotropic glutamate receptor, excitotoxicity, N-Acetyl-Apartyl Glutamate (NAAG), stroke, Alzheimer's, Disease, Alzheimer's Disease, Schizophrenia, Multiple Sclerosis
Current Medicinal Chemistry
Title: Glutamate in CNS Neurodegeneration and Cognition and its Regulation by GCPII Inhibition
Volume: 19 Issue: 9
Author(s): K. A. Rahn, B. S. Slusher and A. I. Kaplin
Affiliation:
Keywords: Glutamate, neurodegeneration, cognitive impairment, Glutamate Carboxypeptidase II (GCPII), NAAG peptidase, NAALADase, metabotropic glutamate receptor, ionotropic glutamate receptor, excitotoxicity, N-Acetyl-Apartyl Glutamate (NAAG), stroke, Alzheimer's, Disease, Alzheimer's Disease, Schizophrenia, Multiple Sclerosis
Abstract: Glutamate, first identified in 1866, is the primary excitatory neurotransmitter in the brain. While it is critically important in many highly regulated cortical functions such as learning and memory, glutamate can be much like the magic the Sorcerers Apprentice used in Goethes poem: when conjured under unregulated conditions glutamate can get quickly out of control and lead to deleterious consequences. Two broad types of glutamate receptors, the ionotropic and metabotropic, facilitate glutamatergic neurotransmission in the CNS and play key roles in regulating cognitive function. Excessive activation of these receptors leads to excitotoxicity, especially in brain regions that are developmentally and regionally vulnerable to this kind of injury. Dysregulation of glutamate signaling leads to neurodegeneration that plays a role in a number of neuropsychiatric diseases, prompting the development and utilization of novel strategies to balance the beneficial and deleterious potential of this important neurotransmitter. Inhibition of the enzyme glutamate carboxypeptidase II (GCPII) is one method of manipulating glutamate neurotransmission. Positive outcomes (decreased neuronal loss, improved cognition) have been demonstrated in preclinical models of ALS, stroke, and Multiple Sclerosis due to inhibition of GCPII, suggesting this method of glutamate regulation could serve as a therapeutic means for treating neurodegeneration and cognitive impairment.
Export Options
About this article
Cite this article as:
A. Rahn K., S. Slusher B. and I. Kaplin A., Glutamate in CNS Neurodegeneration and Cognition and its Regulation by GCPII Inhibition, Current Medicinal Chemistry 2012; 19 (9) . https://dx.doi.org/10.2174/092986712799462649
DOI https://dx.doi.org/10.2174/092986712799462649 |
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
-
Molecular and Biological Aspects of the Bovine Immunodeficiency Virus
Current HIV Research The Potential of Secondary Metabolites from Plants as Drugs or Leads Against Protozoan Neglected Diseases – Part I
Current Medicinal Chemistry Microglia Phenotype Diversity
CNS & Neurological Disorders - Drug Targets Recent Advances on the Roles of NO in Cancer and Chronic Inflammatory Disorders
Current Medicinal Chemistry General Anesthetics in Brain Injury: Friends or Foes?
Current Pharmaceutical Design Oncotarget Strategies For Herpes Simplex Virus-1
Current Gene Therapy West Nile Virus Vaccine.
Current Drug Targets - Infectious Disorders Potential Factors Induced by Filoviruses that Lead to Immune Supression
Current Molecular Medicine Cosignaling Molecules Around LIGHT-HVEM-BTLA: From Immune Activation to Therapeutic Targeting
Current Molecular Medicine Synthetic and Natural Immunomodulators Acting as Interferon Inducers
Current Pharmaceutical Design Pre-Clinical Considerations in the Assessment of Immunogenicity for Protein Therapeutics
Current Drug Safety Directing the Antiretroviral Drugs to the Brain Reservoir: A Nanoformulation Approach for NeuroAIDS
Current Drug Metabolism Chimeric T Helper-B Cell Peptides Induce Protective Response Against Japanese Encephalitis Virus in Mice
Protein & Peptide Letters Clinical Significance of Cytokines and Chemokines in Neuropsychiatric Systemic Lupus Erythematosus
Current Rheumatology Reviews The Pulse of Drug Development for Alzheimers Disease
Reviews on Recent Clinical Trials Childhood Infectious Encephalitis: An Overview of Clinical Features, Investigations, Treatment, and Recent Patents
Recent Patents on Inflammation & Allergy Drug Discovery The Contrasting Roles of NKT Cells in Tumor Immunity
Current Molecular Medicine SARS-CoV-2 Proteins: Are They Useful as Targets for COVID-19 Drugs and Vaccines?
Current Molecular Medicine Drug Targets for Rational Design against Emerging Coronaviruses
Infectious Disorders - Drug Targets MRI of Central Nervous System (CNS) Vasculitis
Current Medical Imaging