title: Alternative Fuels in Epilepsy and Amyotrophic Lateral Sclerosis.
abstract: This review summarises the recent findings on metabolic treatments for epilepsy and Amyotrophic Lateral Sclerosis (ALS) in honour of Professor Ursula Sonnewald. The metabolic impairments in rodent models of these disorders as well as affected patients are being discussed. In both epilepsy and ALS, there are defects in glucose uptake and reduced tricarboxylic acid (TCA) cycling, at least in part due to reduced amounts of C4 TCA cycle intermediates. In addition there are impairments in glycolysis in ALS. A reduction in glucose uptake can be addressed by providing the brain with alternative fuels, such as ketones or medium-chain triglycerides. As anaplerotic fuels, such as the triglyceride of heptanoate, triheptanoin, refill the TCA cycle C4/C5 intermediate pool that is deficient, they are ideal to boost TCA cycling and thus the oxidative metabolism of all fuels.
authors.affiliation: Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, Skerman Building 65, St Lucia, QLD, 4072, Australia.
authors.forename: Tesfaye W
authors.initials: TW
authors.lastname: Tefera
authors.affiliation: Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, Skerman Building 65, St Lucia, QLD, 4072, Australia.
authors.forename: Kah Ni
authors.initials: KN
authors.lastname: Tan
authors.affiliation: Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, Skerman Building 65, St Lucia, QLD, 4072, Australia.
authors.forename: Tanya S
authors.initials: TS
authors.lastname: McDonald
authors.affiliation: Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, Skerman Building 65, St Lucia, QLD, 4072, Australia. k.borges@uq.edu.au.
authors.forename: Karin
authors.identifier: http://orcid.org/0000-0001-7448-0770
authors.initials: K
authors.lastname: Borges
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000178:diet therapy* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D055423:Diet, Ketogenic / Q000379:methods; D004827:Epilepsy / Q000178:diet therapy* / Q000378:metabolism*; D005227:Fatty Acids / Q000008:administration & dosage / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D014280:Triglycerides / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D014280:Triglycerides; C531010:triheptanoin
keywords: ALS; Anaplerosis; Epilepsy; Glycolysis; Ketogenic diet; Medium chain triglyceride; Tricarboxylic acid cycle; Triheptanoin