Neuroketotherapeutics: A modern review of a century-old therapy. (July 2018)

• Record Type: Journal Article
• Authors: Koppel, Scott J.; Swerdlow, Russell H.
• Is Part Of: Neurochemistry international. Volume 117(2018)
• Page Start: 114
• Page End: 125
• Publication Date: 2018-07
• Subjects: Ketone bodies -- Ketogenic diet -- β-hydroxybutyrate -- Bioenergetics -- Alzheimer's disease -- Mitochondria; 2-DG 2-deoxy-d-glucose -- Aβ amyloid-β -- Acetyl-CoA acetyl-coenzyme A -- ADP adenosine diphosphate -- Akt protein kinase B -- AD Alzheimer's disease -- ALS amyotrophic lateral sclerosis -- AMP adenosine monophosphate -- APP amyloid precursor protein -- ANLS astrocyte-neuron lactate shuttle -- ATP adenosine triphosphate -- BDNF brain derived neurotrophic factor -- BHB β-hydroxybutyrate -- BHD1 β-hydroxybutyrate dehydrogenase 1 -- cAMP cyclic AMP -- CNS central nervous system -- CREB cAMP response element-binding protein -- CREM cAMP response element modulatory protein -- CTE chronic traumatic encephalopathy -- DAG diacylglycerol -- EAE experimental autoimmune encephalomyelitis -- ETC electron transport chain -- FADH2 flavin adenine dinucleotide -- FDG-PET fluorodeoxyglucose positron emission tomography -- FFA3 free fatty acid receptor 3 -- FTD frontotemporal dementia -- GABA γ-aminobutyric acid -- GCL glutamate cysteine ligase -- GPR G-coupled protein receptor -- GSH glutathione -- GSK-3β glycogen synthase kinase-3β -- HCA2 hydrocarboxylic acid receptor 2 -- HD Huntington's disease -- HDAC histone deacetylase -- HMG-CoA β-hydroxy-β-methylglutaryl-coenzyme A -- H2O2 hydrogen peroxide -- IP3 inositol 1, 4, 5-triphosphate -- KAT lysine acetyl-transferase -- KATP ATP-sensitive potassium channels -- KD ketogenic diet -- KE ketone ester -- Kir potassium inward rectifier channel -- KV voltage sensitive potassium channel -- LTP long term potentiation -- MAPK mitogen activated protein kinase -- MCAO middle cerebral artery occlusion -- MCT medium chain triglyceride -- MnSOD manganese superoxide dismutase -- MPP+ 1-methyl-4-phenylpyridinium -- MS multiple sclerosis -- mTORC mammalian target of rapamycin complex -- NADH nicotinamide adenine dinucleotide -- NF-κB nuclear factor kappa-light chain-enhancer of activated B cells -- NG1 neuregulin 1 -- NGF nerve growth factor -- NMDA N-methyl-d-aspartate -- NP-3 3-nitroproprionic acid -- Nrf2 nuclear factor erythroid 2-related factor -- OXCT1 3-oxoacid coenzyme A transferase 1 -- PD Parkinson's disease -- PKC protein kinase C -- PLCβ phospholipase-C β -- PLCγ phospholipase-C γ -- PPARγ peroxisome proliferator activated receptor-γ -- PTM post-translational modification -- RONS reactive oxygen nitrogen species -- SCOT succinyl-coenzyme A:3-ketoacid transferase -- Sirt Sirtuin -- SNpc substantia nigra pars compacta -- SNpr substantia nigra pars reticulata -- TBI traumatic brain injury -- TCA tricarboxylic acid -- TDP-43 transactive response DNA binding protein 43 kDa -- TSC tuberous sclerosis -- UCP uncoupling protein -- UPDRS unified Parkinson's disease rating scale -- VMH ventromedial hypothalamus; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2017.05.019
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: Neuroketotherapeutics represent a class of bioenergetic medicine therapies that feature the induction of ketosis. These therapies include medium-chain triglyceride supplements, ketone esters, fasting, strenuous exercise, the modified Atkins diet, and the classic ketogenic diet. Extended experience reveals persons with epilepsy, especially pediatric epilepsy, benefit from ketogenic diets although the mechanisms that underlie its effects remain unclear. Data indicate ketotherapeutics enhance mitochondrial respiration, promote neuronal long-term potentiation, increase BDNF expression, increase GPR signaling, attenuate oxidative stress, reduce inflammation, and alter protein post-translational modifications via lysine acetylation and β-hydroxybutyrylation. These properties have further downstream implications involving Akt, PLCγ, CREB, Sirtuin, and mTORC pathways. Further studies of neuroketotherapeutics will enhance our understanding of ketone body molecular biology, and reveal novel central nervous system therapeutic applications. Highlights: Several approaches exist for achieving ketosis. Ketosis approaches produce pervasive molecular effects. These approaches may potentially benefit multiple neurologic conditions.