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PERSPECTIVE article

Front. Mol. Neurosci.
Sec. Neuroplasticity and Development
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1465013
This article is part of the Research Topic Latest Advances in Neuroscience at the 9th Croatian Neuroscience Congress View all 10 articles

The good, the bad, and the unknown nature of decreased GD3 synthase expression

Provisionally accepted
Borna Puljko Borna Puljko 1*Josip Grbavac Josip Grbavac 2Vinka Potočki Vinka Potočki 3Katarina Ilic Katarina Ilic 4Barbara Viljetić Barbara Viljetić 2*Svjetlana Kalanj Bognar Svjetlana Kalanj Bognar 1Marija Heffer Marija Heffer 5Željko Debeljak Željko Debeljak 6*Senka Blažetić Senka Blažetić 7*Kristina Mlinac-Jerkovic Kristina Mlinac-Jerkovic 1,8*
  • 1 Croatian Institute for Brain Research and Department of Chemistry and Biochemistry, School of Medicine, University of Zagreb, Zagreb, Croatia
  • 2 Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
  • 3 Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia
  • 4 BRAIN Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
  • 5 Department of Medical Biology and Genetics, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Osijek, Croatia
  • 6 Department of Pharmacology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek and Clinical Institute of Laboratory Diagnostics, Osijek University Hospital, Osijek, Croatia
  • 7 Department of Biology, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
  • 8 School of Medicine, University of Zagreb, Zagreb, Croatia

The final, formatted version of the article will be published soon.

    This paper explores the physiological consequences of decreased expression of GD3 synthase (GD3S), a biosynthetic enzyme that catalyzes the synthesis of b-series gangliosides. GD3S is a key factor in tumorigenesis, with overexpression enhancing tumor growth, proliferation, and metastasis in various cancers. Hence, inhibiting GD3S activity has potential therapeutic effects due to its role in malignancyassociated pathways across different cancer types. GD3S has also been investigated as a promising therapeutic target in treatment of various neurodegenerative disorders. Drugs targeting GD3 and GD3S have been extensively explored and underwent clinical trials, however decreased GD3S expression in mouse models, human subjects, and in vitro studies has demonstrated serious adverse effects. We highlight these negative consequences and show original mass spectrometry imaging (MSI) data indicating that inactivated GD3S can generally negatively affect energy metabolism, regulatory pathways, and mitigation of oxidative stress. The disturbance in several physiological systems induced by GD3S inhibition underscores the vital role of this enzyme in maintaining cellular homeostasis and should be taken into account when GD3S is considered as a therapeutic target.

    Keywords: ST8SIA1, Gangliosides, Glycosphingolipids, Lipid Metabolism, lipidomics

    Received: 15 Jul 2024; Accepted: 04 Nov 2024.

    Copyright: © 2024 Puljko, Grbavac, Potočki, Ilic, Viljetić, Kalanj Bognar, Heffer, Debeljak, Blažetić and Mlinac-Jerkovic. 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) or licensor 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.

    * Correspondence:
    Borna Puljko, Croatian Institute for Brain Research and Department of Chemistry and Biochemistry, School of Medicine, University of Zagreb, Zagreb, Croatia
    Barbara Viljetić, Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
    Željko Debeljak, Department of Pharmacology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek and Clinical Institute of Laboratory Diagnostics, Osijek University Hospital, Osijek, Croatia
    Senka Blažetić, Department of Biology, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
    Kristina Mlinac-Jerkovic, School of Medicine, University of Zagreb, Zagreb, Croatia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.