The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis

Gliomas are highly aggressive primary brain tumors, with glioblastoma multiforme being the most severe and the most common one. Aberrations in sphingolipid metabolism are a hallmark of glioma cells. The sphingolipid rheostat represents the balance between the pro-apoptotic ceramide and pro-survival...

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Main Authors: Ivana Karmelić, Mia Jurilj Sajko, Tomislav Sajko, Krešimir Rotim, Dragana Fabris
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2024.1466141/full
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author Ivana Karmelić
Mia Jurilj Sajko
Tomislav Sajko
Krešimir Rotim
Dragana Fabris
author_facet Ivana Karmelić
Mia Jurilj Sajko
Tomislav Sajko
Krešimir Rotim
Dragana Fabris
author_sort Ivana Karmelić
collection DOAJ
description Gliomas are highly aggressive primary brain tumors, with glioblastoma multiforme being the most severe and the most common one. Aberrations in sphingolipid metabolism are a hallmark of glioma cells. The sphingolipid rheostat represents the balance between the pro-apoptotic ceramide and pro-survival sphingosine-1-phosphate (S1P), and in gliomas it is shifted toward cell survival and proliferation, promoting gliomas’ aggressiveness, cellular migration, metastasis, and invasiveness. The sphingolipid rheostat can be altered by targeting enzymes that directly or indirectly affect the ratio of ceramide to S1P, leading to increased ceramide or decreased S1P levels. Targeting the sphingolipid rheostat offers a potential therapeutic pathway for glioma treatment which can be considered through reducing S1P levels or modulating S1P receptors to reduce cell proliferation, as well as through increasing ceramide levels to induce apoptosis in glioma cells. Although the practical translation into clinical therapy is still missing, sphingolipid rheostat targeting in gliomas has been of great research interest in recent years with several interesting achievements in the glioma therapy approach, offering hope for patients suffering from these vicious malignancies.
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spelling doaj-art-a3e5ada97dc04a5c8c69c59022604ca32025-08-20T01:54:54ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2024-12-011210.3389/fcell.2024.14661411466141The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesisIvana Karmelić0Mia Jurilj Sajko1Tomislav Sajko2Krešimir Rotim3Dragana Fabris4Department of Medical Chemistry, Biochemistry and Clinical Chemistry, School of Medicine, University of Zagreb, Zagreb, CroatiaDepartment of Neurosurgery, University Hospital Center “Sestre milosrdnice”, Zagreb, CroatiaDepartment of Neurosurgery, University Hospital Center “Sestre milosrdnice”, Zagreb, CroatiaDepartment of Neurosurgery, University Hospital Center “Sestre milosrdnice”, Zagreb, CroatiaDepartment of Medical Chemistry, Biochemistry and Clinical Chemistry, School of Medicine, University of Zagreb, Zagreb, CroatiaGliomas are highly aggressive primary brain tumors, with glioblastoma multiforme being the most severe and the most common one. Aberrations in sphingolipid metabolism are a hallmark of glioma cells. The sphingolipid rheostat represents the balance between the pro-apoptotic ceramide and pro-survival sphingosine-1-phosphate (S1P), and in gliomas it is shifted toward cell survival and proliferation, promoting gliomas’ aggressiveness, cellular migration, metastasis, and invasiveness. The sphingolipid rheostat can be altered by targeting enzymes that directly or indirectly affect the ratio of ceramide to S1P, leading to increased ceramide or decreased S1P levels. Targeting the sphingolipid rheostat offers a potential therapeutic pathway for glioma treatment which can be considered through reducing S1P levels or modulating S1P receptors to reduce cell proliferation, as well as through increasing ceramide levels to induce apoptosis in glioma cells. Although the practical translation into clinical therapy is still missing, sphingolipid rheostat targeting in gliomas has been of great research interest in recent years with several interesting achievements in the glioma therapy approach, offering hope for patients suffering from these vicious malignancies.https://www.frontiersin.org/articles/10.3389/fcell.2024.1466141/fulldiffuse gliomaglioblastomasphingosine-1-phosphateceramidessphingolipid rheostat
spellingShingle Ivana Karmelić
Mia Jurilj Sajko
Tomislav Sajko
Krešimir Rotim
Dragana Fabris
The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis
Frontiers in Cell and Developmental Biology
diffuse glioma
glioblastoma
sphingosine-1-phosphate
ceramides
sphingolipid rheostat
title The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis
title_full The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis
title_fullStr The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis
title_full_unstemmed The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis
title_short The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis
title_sort role of sphingolipid rheostat in the adult type diffuse glioma pathogenesis
topic diffuse glioma
glioblastoma
sphingosine-1-phosphate
ceramides
sphingolipid rheostat
url https://www.frontiersin.org/articles/10.3389/fcell.2024.1466141/full
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