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Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema

Human malignant brain tumors such as gliomas are devastating due to the induction of cerebral edema and neurodegeneration. A major contributor to glioma-induced neurodegeneration has been identified as glutamate. Glutamate promotes cell growth and proliferation in variety of tumor types. Intriguentl...

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Autores principales: Yakubov, Eduard, Schmid, Sebastian, Hammer, Alexander, Chen, Daishi, Dahlmanns, Jana Katharina, Mitrovic, Ivana, Zurabashvili, Luka, Savaskan, Nicolai, Steiner, Hans-Herbert, Dahlmanns, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406130/
https://www.ncbi.nlm.nih.gov/pubmed/37554158
http://dx.doi.org/10.3389/fonc.2023.1176038
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author Yakubov, Eduard
Schmid, Sebastian
Hammer, Alexander
Chen, Daishi
Dahlmanns, Jana Katharina
Mitrovic, Ivana
Zurabashvili, Luka
Savaskan, Nicolai
Steiner, Hans-Herbert
Dahlmanns, Marc
author_facet Yakubov, Eduard
Schmid, Sebastian
Hammer, Alexander
Chen, Daishi
Dahlmanns, Jana Katharina
Mitrovic, Ivana
Zurabashvili, Luka
Savaskan, Nicolai
Steiner, Hans-Herbert
Dahlmanns, Marc
author_sort Yakubov, Eduard
collection PubMed
description Human malignant brain tumors such as gliomas are devastating due to the induction of cerebral edema and neurodegeneration. A major contributor to glioma-induced neurodegeneration has been identified as glutamate. Glutamate promotes cell growth and proliferation in variety of tumor types. Intriguently, glutamate is also an excitatory neurotransmitter and evokes neuronal cell death at high concentrations. Even though glutamate signaling at the receptor and its downstream effectors has been extensively investigated at the molecular level, there has been little insight into how glutamate enters the tumor microenvironment and impacts on metabolic equilibration until recently. Surprisingly, the 12 transmembrane spanning tranporter xCT (SLC7A11) appeared to be a major player in this process, mediating glutamate secretion and ferroptosis. Also, PPARγ is associated with ferroptosis in neurodegeneration, thereby destroying neurons and causing brain swelling. Although these data are intriguing, tumor-associated edema has so far been quoted as of vasogenic origin. Hence, glutamate and PPARγ biology in the process of glioma-induced brain swelling is conceptually challenging. By inhibiting xCT transporter or AMPA receptors in vivo, brain swelling and peritumoral alterations can be mitigated. This review sheds light on the role of glutamate in brain tumors presenting the conceptual challenge that xCT disruption causes ferroptosis activation in malignant brain tumors. Thus, interfering with glutamate takes center stage in forming the basis of a metabolic equilibration approach.
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spelling pubmed-104061302023-08-08 Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema Yakubov, Eduard Schmid, Sebastian Hammer, Alexander Chen, Daishi Dahlmanns, Jana Katharina Mitrovic, Ivana Zurabashvili, Luka Savaskan, Nicolai Steiner, Hans-Herbert Dahlmanns, Marc Front Oncol Oncology Human malignant brain tumors such as gliomas are devastating due to the induction of cerebral edema and neurodegeneration. A major contributor to glioma-induced neurodegeneration has been identified as glutamate. Glutamate promotes cell growth and proliferation in variety of tumor types. Intriguently, glutamate is also an excitatory neurotransmitter and evokes neuronal cell death at high concentrations. Even though glutamate signaling at the receptor and its downstream effectors has been extensively investigated at the molecular level, there has been little insight into how glutamate enters the tumor microenvironment and impacts on metabolic equilibration until recently. Surprisingly, the 12 transmembrane spanning tranporter xCT (SLC7A11) appeared to be a major player in this process, mediating glutamate secretion and ferroptosis. Also, PPARγ is associated with ferroptosis in neurodegeneration, thereby destroying neurons and causing brain swelling. Although these data are intriguing, tumor-associated edema has so far been quoted as of vasogenic origin. Hence, glutamate and PPARγ biology in the process of glioma-induced brain swelling is conceptually challenging. By inhibiting xCT transporter or AMPA receptors in vivo, brain swelling and peritumoral alterations can be mitigated. This review sheds light on the role of glutamate in brain tumors presenting the conceptual challenge that xCT disruption causes ferroptosis activation in malignant brain tumors. Thus, interfering with glutamate takes center stage in forming the basis of a metabolic equilibration approach. Frontiers Media S.A. 2023-07-24 /pmc/articles/PMC10406130/ /pubmed/37554158 http://dx.doi.org/10.3389/fonc.2023.1176038 Text en Copyright © 2023 Yakubov, Schmid, Hammer, Chen, Dahlmanns, Mitrovic, Zurabashvili, Savaskan, Steiner and Dahlmanns https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Yakubov, Eduard
Schmid, Sebastian
Hammer, Alexander
Chen, Daishi
Dahlmanns, Jana Katharina
Mitrovic, Ivana
Zurabashvili, Luka
Savaskan, Nicolai
Steiner, Hans-Herbert
Dahlmanns, Marc
Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema
title Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema
title_full Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema
title_fullStr Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema
title_full_unstemmed Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema
title_short Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema
title_sort ferroptosis and ppar-gamma in the limelight of brain tumors and edema
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406130/
https://www.ncbi.nlm.nih.gov/pubmed/37554158
http://dx.doi.org/10.3389/fonc.2023.1176038
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