title: A novel treatment strategy for glioblastoma multiforme and glioma associated seizures: increasing glutamate uptake with PPARγ agonists.
abstract: The established role of glutamate in the pathogenesis of glioma-associated seizures (GAS) led us to investigate a novel treatment method using an established drug class, peroxisome proliferator activated receptor (PPAR) gamma agonists. Previously, sulfasalazine has been shown to prevent release of glutamate from glioma cells and prevent GAS in rodent models. However, raising protein mediated glutamate transport via excitatory amino acid transporter 2 (EAAT2) has not been investigated previously to our knowledge. PPAR gamma agonists are known to upregulate functional EAAT2 expression in astrocytes and prevent excitotoxicity caused by glutamate excess. These agents are also known to have anti-neoplastic mechanisms. Herein we discuss and review the potential mechanisms of these drugs and highlight a novel potential treatment for GAS.
authors.affiliation: Department of Surgery, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, UK. Electronic address: jared.ching@nhs.net.
authors.forename: Jared
authors.initials: J
authors.lastname: Ching
authors.affiliation: Department of Surgery, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Amiridis
authors.affiliation: Department of Surgery, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: Stanley S
authors.initials: SS
authors.lastname: Stylli
authors.affiliation: Department of Surgery, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morokoff
authors.affiliation: Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia.
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
authors.affiliation: Department of Surgery, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Kaye
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005909:Glioblastoma / Q000150:complications / Q000188:drug therapy*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000970:Antineoplastic Agents; D027342:Excitatory Amino Acid Transporter 2; D047495:PPAR gamma; D018698:Glutamic Acid
keywords: Glioma; Glutamate; PPAR gamma; Seizures