Abstract
Extensive nerve cell death occurs during the development of the central nervous system as well as in episodes of trauma and in neurodegenerative disease. The mechanistic details of how these cells die are poorly understood. Here we describe a unique oxidative stress-induced programmed cell death pathway called oxytosis, and outline pharmacological approaches which interfere with its execution. Oxidative glutamate toxicity, in which exogenous glutamate inhibits cystine uptake through the cystine/glutamate antiporter leading to a depletion of glutathione, is used as an example of oxytosis. It is shown that there is a sequential requirement for de novo macromolecular synthesis, lipoxygenase activation, reactive oxygen species production, and the opening of cGMP-gated channels which allow the influx of extracellular calcium. The translation initiation factor eIF2α plays a central role in this pathway by regulating the levels of glutathione. Finally, examples are given in which the reduction in glutathione, the production of reactive oxygen species, and calcium influx can be experimentally manipulated to prevent cell death. Data are reviewed which suggest that oxytosis may be involved in nerve cell death associated with nervous system trauma and disease.
Current Topics in Medicinal Chemistry
Title: Oxytosis: A Novel Form of Programmed Cell Death
Volume: 1 Issue: 6
Author(s): Shirlee Tan, David Schubert and Pamela Maher
Affiliation:
Abstract: Extensive nerve cell death occurs during the development of the central nervous system as well as in episodes of trauma and in neurodegenerative disease. The mechanistic details of how these cells die are poorly understood. Here we describe a unique oxidative stress-induced programmed cell death pathway called oxytosis, and outline pharmacological approaches which interfere with its execution. Oxidative glutamate toxicity, in which exogenous glutamate inhibits cystine uptake through the cystine/glutamate antiporter leading to a depletion of glutathione, is used as an example of oxytosis. It is shown that there is a sequential requirement for de novo macromolecular synthesis, lipoxygenase activation, reactive oxygen species production, and the opening of cGMP-gated channels which allow the influx of extracellular calcium. The translation initiation factor eIF2α plays a central role in this pathway by regulating the levels of glutathione. Finally, examples are given in which the reduction in glutathione, the production of reactive oxygen species, and calcium influx can be experimentally manipulated to prevent cell death. Data are reviewed which suggest that oxytosis may be involved in nerve cell death associated with nervous system trauma and disease.
Export Options
About this article
Cite this article as:
Shirlee Tan , David Schubert and Pamela Maher , Oxytosis: A Novel Form of Programmed Cell Death, Current Topics in Medicinal Chemistry 2001; 1 (6) . https://dx.doi.org/10.2174/1568026013394741
DOI https://dx.doi.org/10.2174/1568026013394741 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...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
-
Immunomodulation Mechanism of Antidepressants: Interactions between Serotonin/Norepinephrine Balance and Th1/Th2 Balance
Current Neuropharmacology Multi-Target Directed Drugs: A Modern Approach for Design of New Drugs for the treatment of Alzheimer’s Disease
Current Neuropharmacology Approaching Neurological Diseases to Reduce Mobility Limitations in Older Persons
Current Pharmaceutical Design Meet Our Editorial Board Member:
Current Alzheimer Research Nanotechnology-based Targeting of Neurodegenerative Disorders: A Promising Tool for Efficient Delivery of Neuromedicines
Current Drug Targets The Future of Neuroregenerative Therapy for Parkinson’s Disease
Current Tissue Engineering (Discontinued) Stem Cell Pharmacogenomics
Current Topics in Medicinal Chemistry Neurodegeneration in the Brain Tumor Microenvironment: Glutamate in the Limelight
Current Neuropharmacology Dietary Approaches and Supplements in the Prevention of Cognitive Decline and Alzheimer's Disease
Current Pharmaceutical Design Clinical Neurophysiology of Brain Plasticity in Aging Brain
Current Pharmaceutical Design Nanoparticle Coated Viral Vectors for Gene Therapy
Current Biotechnology Innovative Anthocyanin/Anthocyanidin Formulation Protects SK-N-SH Cells Against the Amyloid-β Peptide-Induced Toxicity: Relevance to Alzheimer’s Disease
Central Nervous System Agents in Medicinal Chemistry Pharmacogenetics of Parkinson’s Disease – Through Mechanisms of Drug Actions
Current Genomics Post-Translational Protein Modifications of Rare and Unconventional Types: Implications in Functions and Diseases
Current Medicinal Chemistry Advances in Drug Delivery from Nose to Brain: An Overview
Current Drug Therapy Biomarkers and Cellular Signal Detection for Alzheimer’s Disease, Stroke, and Immune System Mediated Disorders
Current Neurovascular Research A Synopsis on the Role of Tyrosine Hydroxylase in Parkinson’s Disease
CNS & Neurological Disorders - Drug Targets Colostral Proline-Rich Polypeptides - Immunoregulatory Properties and Prospects of Therapeutic Use in Alzheimers Disease
Current Alzheimer Research Non-Demented Individuals with Alzheimer’s Disease Neuropathology: Resistance to Cognitive Decline May Reveal New Treatment Strategies
Current Pharmaceutical Design Neurotrophic Factors for Retinal Ganglion Cell Neuropathy - With a Special Reference to Diabetic Neuropathy in the Retina
Current Diabetes Reviews