Abstract
Regionally specific neuronal loss is a distinguishing feature of Alzheimer disease (AD). Excitotoxicity is a mechanism commonly invoked to explain this. We review the accumulating evidence for such a hypothesis, particularly the altered expression and pharmacology of glutamate receptors and transporters in pathologically susceptible regions of the AD brain. Loss of neurons would be expected to lead to the retrograde degeneration of their afferents, which should be reflected in a loss of presynaptic markers such as synaptophysin. We discuss the possibility that neurons may be destroyed locally, but that glutamatergic presynaptic terminals may remain, or even re-proliferate. The reduced glutamate uptake site density in AD brain may signify a loss of the transporters on otherwise intact terminals, rather than the loss of glutamatergic afferents. Neuronal death may follow if cells are exposed to excessive amounts of glutamate; the loss of transporters from functioning, but defective, glutamate termin als would mean they could continue to release glutamate to exacerbate excitotoxicity. We discuss experimental methods to quantitate synapses, which are crucial for deciding between the various possibilities.
Keywords: Excitatory Amino Acids, Neurotoxicity, Cerebral Cortex, Glutamate - Receptors, Glutamate - Transporters, Synaptic Terminals, Neurodegenerative Diseases
Current Alzheimer Research
Title: The Identification and Characterization of Excitotoxic Nerve-endings in Alzheimer Disease
Volume: 1 Issue: 1
Author(s): Rudi K. Tannenberg, Heather L. Scott, Robert I. Westphalen and Peter R. Dodd
Affiliation:
Keywords: Excitatory Amino Acids, Neurotoxicity, Cerebral Cortex, Glutamate - Receptors, Glutamate - Transporters, Synaptic Terminals, Neurodegenerative Diseases
Abstract: Regionally specific neuronal loss is a distinguishing feature of Alzheimer disease (AD). Excitotoxicity is a mechanism commonly invoked to explain this. We review the accumulating evidence for such a hypothesis, particularly the altered expression and pharmacology of glutamate receptors and transporters in pathologically susceptible regions of the AD brain. Loss of neurons would be expected to lead to the retrograde degeneration of their afferents, which should be reflected in a loss of presynaptic markers such as synaptophysin. We discuss the possibility that neurons may be destroyed locally, but that glutamatergic presynaptic terminals may remain, or even re-proliferate. The reduced glutamate uptake site density in AD brain may signify a loss of the transporters on otherwise intact terminals, rather than the loss of glutamatergic afferents. Neuronal death may follow if cells are exposed to excessive amounts of glutamate; the loss of transporters from functioning, but defective, glutamate termin als would mean they could continue to release glutamate to exacerbate excitotoxicity. We discuss experimental methods to quantitate synapses, which are crucial for deciding between the various possibilities.
Export Options
About this article
Cite this article as:
Tannenberg K. Rudi, Scott L. Heather, Westphalen I. Robert and Dodd R. Peter, The Identification and Characterization of Excitotoxic Nerve-endings in Alzheimer Disease, Current Alzheimer Research 2004; 1 (1) . https://dx.doi.org/10.2174/1567205043480591
DOI https://dx.doi.org/10.2174/1567205043480591 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
Metabolic Fate of Endocannabinoids
Current Neuropharmacology Utilization of Lipid-based Nanoparticles to Improve the Therapeutic Benefits of Bortezomib
Anti-Cancer Agents in Medicinal Chemistry Anticancer Agents: VTA or VDA
Current Bioactive Compounds Human Sirtuins: An Overview of an Emerging Drug Target in Age-Related Diseases and Cancer
Current Drug Targets Liposomal Formulation of Monovalent Cholesteryl Cytofectins with Acyclic Head Groups and Gene Delivery: A Systematic Review
Current Pharmaceutical Biotechnology A New Investigational Perspective for Purines Against Glioblastoma Invasiveness
Current Drug Targets An Overview of Phenserine Tartrate, A Novel Acetylcholinesterase Inhibitor for the Treatment of Alzheimers Disease
Current Alzheimer Research Voltage-Gated Ion Channels, New Targets in Anti-Cancer Research
Recent Patents on Anti-Cancer Drug Discovery Role of the Renin-Angiotensin-Aldosterone System in the Pathogenesis of Atherosclerosis
Current Pharmaceutical Design NMDA Receptors in Glial Cells: Pending Questions
Current Neuropharmacology Oligonucleotides and G-quadruplex Stabilizers: Targeting Telomeres and Telomerase in Cancer Therapy
Current Pharmaceutical Design Insights into Immunophilin Structure and Function
Current Medicinal Chemistry Mechanisms Underlying Chemopreventive Effects of Flavonoids via Multiple Signaling Nodes within Nrf2-ARE and AhR-XRE Gene Regulatory Networks
Current Chemical Biology Immune-Inflammatory Responses and Oxidative Stress in Alzheimers Disease: Therapeutic Implications
Current Pharmaceutical Design New Approaches to Target Cancer Stem Cells: Current Scenario
Mini-Reviews in Medicinal Chemistry Cellular and Biochemical Alterations Caused by Artificial Depletion of Glutathione
Current Enzyme Inhibition Thrombospondin and Apoptosis: Molecular Mechanisms and Use for Design of Complementation Treatments
Current Drug Targets Pathophysiological Roles of Transglutaminase - Catalyzed Reactions in the Pathogenesis of Human Diseases
Inflammation & Allergy - Drug Targets (Discontinued) Granular Non-Fibrillar Aggregates and Toxicity in Alzheimer’s Disease
Current Alzheimer Research Genotoxicity in Alzheimers Disease: Role of Amyloid
Current Alzheimer Research