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Mitochondrial Dysfunction in Gliomas
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SYSNO ASEP 0423057 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Mitochondrial Dysfunction in Gliomas Author(s) Katsetos, C.D. (US)
Anni, H. (US)
Dráber, Pavel (UMG-J) RID, ORCIDSource Title Seminars in Pediatric Neurology. - : Elsevier - ISSN 1071-9091
Roč. 20, č. 3 (2013), s. 216-227Number of pages 12 s. Language eng - English Country US - United States Keywords gliomas ; mitochondrial dysfunction ; microtubule proteins Subject RIV EB - Genetics ; Molecular Biology R&D Projects LH12050 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UMG-J - RVO:68378050 UT WOS 000328262000007 DOI 10.1016/j.spen.2013.09.003 Annotation Mitochondrial (mt) dysfunction in gliomas has been linked to abnormalities of mt energy metabolism, marked by a metabolic shift from oxidative phosphorylation to glycolysis ("Warburg effect"), disturbances in mt membrane potential regulation and apoptotic signaling, as well as to somatic mutations involving the Krebs cycle enzyme isocitrate dehydrogenase. Evolving biological concepts with potential therapeutic implications include interaction between microtubule proteins and mitochondria (mt) in the control of closure of voltage-dependent anion channels and in the regulation of mt dynamics and the mt-endoplasmic reticulum network. The cytoskeletal protein beta III-tubulin, which is overexpressed in malignant gliomas, has emerged as a prosurvival factor associated in part with nit and also as a marker of chemoresistance. Mt-targeted therapeutic strategies that are discussed include the following: (1) metabolic modulation with emphasis on dichloroacetate, a pyruvate dehydrogenase kinase inhibitor; (2) tumor cell death via apoptosis induced by tricyclic antidepressants, microtubule-modulating drugs, and small molecules or compounds capable of inflicting reactive oxygen species dependent tumor cell death; and (3) pretreatment mt priming and mt-targeted prodrug cancer therapy. (C) 2013 Elsevier Inc. All rights reserved. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2014
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