Exploiting metabolic differences in glioma therapy.

Current Drug Discovery Technologies
Francesca Galeffi, Dennis A Turner

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 tran...Continue Reading

Citations

Mar 20, 2016·Biochimica Et Biophysica Acta·Jhudit Pérez-EscuredoPierre Sonveaux
Dec 18, 2013·Cancer Letters·Vishal Premdev SharmaMichael Eric Geusz
Sep 3, 2016·International Journal of Molecular Sciences·Shiro Koizume, Yohei Miyagi
Jun 18, 2017·Frontiers in Physiology·Alexandre ValléeJean-Noël Vallée
Dec 7, 2017·Journal of Bioenergetics and Biomembranes·Marina ComelliIrene Mavelli

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