Abstract
Brain function depends upon complex metabolic interactions amongst only a few different cell types, with astrocytes providing critical support for neurons. Astrocyte functions include buffering the extracellular space, providing substrates to neurons, interchanging glutamate and glutamine for synaptic transmission with neurons, and facilitating access to blood vessels. Whereas neurons possess highly oxidative metabolism and easily succumb to ischemia, astrocytes rely more on glycolysis and metabolism associated with synthesis of critical intermediates, hence are less susceptible to lack of oxygen. Astrocytoma and higher grade glioma cells demonstrate both basic metabolic mechanisms of astrocytes as well as tumors in general, e.g. they show a high glycolytic rate, lactate extrusion, ability to proliferate even under hypoxia, and opportunistic use of mechanisms to enhance metabolism and blood vessel generation, and suppression of cell death pathways. There may be differences in metabolism between neurons, normal astrocytes and astrocytoma cells, providing therapeutic opportunities against astrocytomas, including a wide range of enzyme and transporter differences, regulation of hypoxia-inducible factor (HIF), glutamate uptake transporters and glutamine utilization, differential sensitivities of monocarboxylate transporters, presence of glycogen, high interlinking with gap junctions, use of NADPH for lipid synthesis, utilizing differential regulation of synthetic enzymes (e.g. isocitrate dehydrogenase, pyruvate carboxylase, pyruvate dehydrogenase, lactate dehydrogenase, malate-aspartate NADH shuttle) and different glucose uptake mechanisms. These unique metabolic susceptibilities may augment conventional therapeutic attacks based on cell division differences and surface receptors alone, and are starting to be implemented in clinical trials.
Keywords: Astrocyte, glycolysis, hypoxia-inducible factor, lactate, metabolism, mitochondria, Glioma, neurons, astrocytoma cells, glutamine
Current Drug Discovery Technologies
Title:Exploiting Metabolic Differences in Glioma Therapy
Volume: 9 Issue: 4
Author(s): Francesca Galeffi and Dennis A. Turner
Affiliation:
Keywords: Astrocyte, glycolysis, hypoxia-inducible factor, lactate, metabolism, mitochondria, Glioma, neurons, astrocytoma cells, glutamine
Abstract: Brain function depends upon complex metabolic interactions amongst only a few different cell types, with astrocytes providing critical support for neurons. Astrocyte functions include buffering the extracellular space, providing substrates to neurons, interchanging glutamate and glutamine for synaptic transmission with neurons, and facilitating access to blood vessels. Whereas neurons possess highly oxidative metabolism and easily succumb to ischemia, astrocytes rely more on glycolysis and metabolism associated with synthesis of critical intermediates, hence are less susceptible to lack of oxygen. Astrocytoma and higher grade glioma cells demonstrate both basic metabolic mechanisms of astrocytes as well as tumors in general, e.g. they show a high glycolytic rate, lactate extrusion, ability to proliferate even under hypoxia, and opportunistic use of mechanisms to enhance metabolism and blood vessel generation, and suppression of cell death pathways. There may be differences in metabolism between neurons, normal astrocytes and astrocytoma cells, providing therapeutic opportunities against astrocytomas, including a wide range of enzyme and transporter differences, regulation of hypoxia-inducible factor (HIF), glutamate uptake transporters and glutamine utilization, differential sensitivities of monocarboxylate transporters, presence of glycogen, high interlinking with gap junctions, use of NADPH for lipid synthesis, utilizing differential regulation of synthetic enzymes (e.g. isocitrate dehydrogenase, pyruvate carboxylase, pyruvate dehydrogenase, lactate dehydrogenase, malate-aspartate NADH shuttle) and different glucose uptake mechanisms. These unique metabolic susceptibilities may augment conventional therapeutic attacks based on cell division differences and surface receptors alone, and are starting to be implemented in clinical trials.
Export Options
About this article
Cite this article as:
Galeffi Francesca and A. Turner Dennis, Exploiting Metabolic Differences in Glioma Therapy, Current Drug Discovery Technologies 2012; 9 (4) . https://dx.doi.org/10.2174/157016312803305906
DOI https://dx.doi.org/10.2174/157016312803305906 |
Print ISSN 1570-1638 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6220 |
Related Books
![](/images/wayfinder.jpg)
- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Codon Swapping of Zinc Finger Nucleases Confers Expression in Primary Cells and <i>In Vivo</i> from a Single Lentiviral Vector
Current Gene Therapy Matching Chelators to Radiometals for Positron Emission Tomography Imaging- Guided Targeted Drug Delivery
Current Drug Targets Gender Disparity in Pediatric Diseases
Current Molecular Medicine Geniposide Attenuates Oligomeric Aβ<sub>1-42</sub>-Induced Inflammatory Response by Targeting RAGE-Dependent Signaling in BV2 Cells
Current Alzheimer Research Annexins as Neuroprotective Agents in the Central Nervous System
Current Medicinal Chemistry - Central Nervous System Agents Current HPLC Methods for Assay of Nano Drug Delivery Systems
Current Topics in Medicinal Chemistry CRISPR-Cas9, A Promising Therapeutic Tool for Cancer Therapy: A Review
Protein & Peptide Letters The Radio-Sensitizing Effect of Pharmacological Concentration of Ascorbic Acid on Human Pancreatic Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Protein Kinase C Isozymes as Potential Targets for Anticancer Therapy
Current Cancer Drug Targets Herpes Simplex Viruses in Antiviral Drug Discovery
Current Pharmaceutical Design Morphology of C6 Glioma Cells on a Water-Repellent Fractal Alkyl Ketene Dimer Surface
Current Nanoscience The Autism Candidate Gene Neurobeachin Encodes a Scaffolding Protein Implicated in Membrane Trafficking and Signaling
Current Molecular Medicine Reduced Serotonin Transporter Levels and Inflammation in the Midbrain Raphe of 12 Month Old APP<sub>swe</sub>/PSEN<sub>1dE9</sub> Mice
Current Alzheimer Research Perspectives/Opinion: ADVANCED MEDICAL IMAGING IN THE ERA OF PERSONALIZED OR PRECISION MEDICINE
Current Medical Imaging Patent Selections
Recent Patents on Inflammation & Allergy Drug Discovery Editorial (Thematic Issue: New Therapeutic Approaches for the Treatment of Glioblastoma)
Current Cancer Drug Targets Recent Developments of 18F-FET PET in Neuro-oncology
Current Medicinal Chemistry Interrelation of Major Depression and Antidepressant Transcriptomics
Current Psychopharmacology Efficacy and Safety of Bevacizumab in Glioblastomas
Current Medicinal Chemistry Astrocyte`s RAGE: More Than Just a Question of Mood
Central Nervous System Agents in Medicinal Chemistry