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Research has primarily focused on mitochondrial toxicity, which can cause death of the vulnerable striatal neurons, but other aspects of metabolism have also been implicated. Most previous studies have been carried out using postmortem human brain or non-human cells. Here, we studied bioenergetics in an induced pluripotent stem cell-based model of the disease. We found decreased adenosine triphosphate (ATP) levels in HD cells compared to controls across differentiation stages and protocols. Proteomics data and multiomics network analysis revealed normal or increased levels of mitochondrial messages and proteins, but lowered expression of glycolytic enzymes. Metabolic experiments showed decreased spare glycolytic capacity in HD neurons, while maximal and spare respiratory capacities driven by oxidative phosphorylation were largely unchanged. ATP levels in HD neurons could be rescued with addition of pyruvate or late glycolytic metabolites, but not earlier glycolytic metabolites, suggesting a role for glycolytic deficits as part of the metabolic disturbance in HD neurons. Pyruvate or other related metabolic supplements could have therapeutic benefit in HD.<\/jats:p>","DOI":"10.1093\/hmg\/ddy430","type":"journal-article","created":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T09:43:07Z","timestamp":1550223787000},"page":"1757-1771","source":"Crossref","is-referenced-by-count":55,"title":["Bioenergetic deficits in Huntington\u2019s disease iPSC-derived neural cells and rescue with glycolytic metabolites"],"prefix":"10.1093","volume":"29","author":[{"name":"The HD iPSC Consortium","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6156-5046","authenticated-orcid":false,"given":"Amanda J","family":"Kedaigle","sequence":"additional","affiliation":[{"name":"Computational and Systems Biology Graduate Program and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Fraenkel","sequence":"additional","affiliation":[{"name":"Computational and Systems Biology Graduate Program and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjit S","family":"Atwal","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Simches Research Building, Cambridge Street, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Simches Research Building, Cambridge Street, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F","family":"Gusella","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Simches Research Building, Cambridge Street, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcy E","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Simches Research Building, Cambridge Street, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia A","family":"Kaye","sequence":"additional","affiliation":[{"name":"Gladstone Institutes and Taube\/Koret Center of Neurodegenerative Disease Research, Roddenberry Stem Cell Research Program, Departments of Neurology and Physiology, University of California, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Finkbeiner","sequence":"additional","affiliation":[{"name":"Gladstone Institutes and Taube\/Koret Center of Neurodegenerative Disease Research, Roddenberry Stem Cell Research Program, Departments of Neurology and Physiology, University of California, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia B","family":"Mattis","sequence":"additional","affiliation":[{"name":"Board of Governors Regenerative Medicine Institute and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colton M","family":"Tom","sequence":"additional","affiliation":[{"name":"Board of Governors Regenerative Medicine Institute and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive","family":"Svendsen","sequence":"additional","affiliation":[{"name":"Board of Governors Regenerative Medicine Institute and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin R","family":"King","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Department of Neurobiology and Behavior, Department of Medicine, Sue and Bill Gross Stem Cell Center and UCI MIND, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumay","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Department of Neurobiology and Behavior, Department of Medicine, Sue and Bill Gross Stem Cell Center and UCI MIND, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer T","family":"Stocksdale","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Department of Neurobiology and Behavior, Department of Medicine, Sue and Bill Gross Stem Cell Center and UCI MIND, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan G","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Department of Neurobiology and Behavior, Department of Medicine, Sue and Bill Gross Stem Cell Center and UCI MIND, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Casale","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Department of Neurobiology and Behavior, Department of Medicine, Sue and Bill Gross Stem Cell Center and UCI MIND, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping H","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Department of Neurobiology and Behavior, Department of Medicine, Sue and Bill Gross Stem Cell Center and UCI MIND, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie M","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Department of Neurobiology and Behavior, Department of Medicine, Sue and Bill Gross Stem Cell Center and UCI MIND, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey S","family":"Akimov","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Departments of Psychiatry, Neurology, Pharmacology, and Neuroscience, Johns Hopkins University School of Medicine, North Wolfe Street, Baltimore, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Ratovitski","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Departments of Psychiatry, Neurology, Pharmacology, and Neuroscience, Johns Hopkins University School of Medicine, North Wolfe Street, Baltimore, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Arbez","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Departments of Psychiatry, Neurology, Pharmacology, and Neuroscience, Johns Hopkins University School of Medicine, North Wolfe Street, Baltimore, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A","family":"Ross","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Departments of Psychiatry, Neurology, Pharmacology, and Neuroscience, Johns Hopkins University School of Medicine, North Wolfe Street, Baltimore, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,3,7]]},"reference":[{"key":"2020072105163843000_ref1","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nrneurol.2014.24","article-title":"Huntington disease: natural history biomarkers and prospects for therapeutics","volume":"10","author":"Ross","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"2020072105163843000_ref2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S1474-4422(10)70245-3","article-title":"Huntington\u2019s disease: from molecular pathogenesis to clinical treatment","volume":"10","author":"Ross","year":"2011","journal-title":"Lancet Neurol."},{"key":"2020072105163843000_ref3","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s\ndisease chromosomes","volume":"72","author":"MacDonald","year":"1993","journal-title":"Cell"},{"key":"2020072105163843000_ref4","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0140-6736(07)60111-1","article-title":"Huntington\u2019s disease","volume":"369","author":"Walker","year":"2007","journal-title":"Lancet"},{"key":"2020072105163843000_ref5","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/B978-0-12-381328-2.00014-6","article-title":"Genetics and neuropathology of Huntington\u2019s disease","volume":"98","author":"Reiner","year":"2011","journal-title":"Int. Rev. Neurobiol."},{"key":"2020072105163843000_ref6","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1111\/bpa.12426","article-title":"Huntington\u2019s disease (HD): the neuropathology of a multisystem neurodegenerative disorder of the human brain","volume":"26","author":"R\u00fcb","year":"2016","journal-title":"Brain Pathol."},{"key":"2020072105163843000_ref7","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.tibs.2013.05.003","article-title":"Huntington\u2019s disease: underlying molecular mechanisms and emerging concepts","volume":"38","author":"Labbadia","year":"2013","journal-title":"Trends Biochem. Sci."},{"key":"2020072105163843000_ref8","doi-asserted-by":"crossref","first-page":"a007476","DOI":"10.1101\/cshperspect.a007476","article-title":"Huntington\u2019s disease","volume":"3","author":"Finkbeiner","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2020072105163843000_ref9","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/B978-0-12-381328-2.00015-8","article-title":"Pathogenic mechanisms in Huntington\u2019s disease","volume":"98","author":"Jones","year":"2011","journal-title":"Int. Rev. Neurobiol."},{"key":"2020072105163843000_ref10","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1002\/mds.25992","article-title":"Metabolism in HD: still a relevant mechanism?","volume":"29","author":"Duan","year":"2014","journal-title":"Mov. Disord."},{"key":"2020072105163843000_ref11","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1172\/JCI45691","article-title":"Energy deficit in Huntington disease: why it matters","volume":"121","author":"Mochel","year":"2011","journal-title":"J. Clin. Invest."},{"key":"2020072105163843000_ref12","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1196\/annals.1427.018","article-title":"Mitochondria and Huntington\u2019s disease pathogenesis","volume":"1147","author":"Browne","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2020072105163843000_ref13","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1212\/WNL.43.12.2689","article-title":"Evidence for impairment of energy metabolism in vivo in Huntington\u2019s disease using localized 1H NMR spectroscopy","volume":"43","author":"Jenkins","year":"1993","journal-title":"Neurology"},{"key":"2020072105163843000_ref14","doi-asserted-by":"crossref","first-page":"4389","DOI":"10.1523\/JNEUROSCI.20-12-04389.2000","article-title":"Neuroprotective effects of creatine in a transgenic mouse model of Huntington\u2019s disease","volume":"20","author":"Ferrante","year":"2000","journal-title":"J. Neurosci."},{"key":"2020072105163843000_ref15","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.cell.2012.02.035","article-title":"Mitochondria: in sickness and in health","volume":"148","author":"Nunnari","year":"2012","journal-title":"Cell"},{"key":"2020072105163843000_ref16","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nature12985","article-title":"Mitochondrial form and function","volume":"505","author":"Friedman","year":"2014","journal-title":"Nature"},{"key":"2020072105163843000_ref17","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1002\/ana.410320408","article-title":"The cortical lesion of Huntington\u2019s disease: further neurochemical characterization, and reproduction of some of the histological and neurochemical features by N-methyl-D-aspartate lesions of rat cortex","volume":"32","author":"Storey","year":"1992","journal-title":"Ann. Neurol."},{"key":"2020072105163843000_ref18","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0006-8993(94)91412-5","article-title":"Malonate produces striatal lesions by indirect NMDA receptor activation","volume":"647","author":"Henshaw","year":"1994","journal-title":"Brain Res."},{"key":"2020072105163843000_ref19","doi-asserted-by":"crossref","first-page":"7105","DOI":"10.1073\/pnas.92.15.7105","article-title":"Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates","volume":"92","author":"Brouillet","year":"1995","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2020072105163843000_ref20","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/321168a0","article-title":"Replication of the neurochemical characteristics of Huntington\u2019s disease by quinolinic acid","volume":"321","author":"Beal","year":"1986","journal-title":"Nature"},{"key":"2020072105163843000_ref21","doi-asserted-by":"crossref","DOI":"10.1155\/2013\/104024","article-title":"Quinolinic acid: an endogenous neurotoxin with multiple targets","volume":"2013","author":"Lugo-Huitr\u00f3n","year":"2013","journal-title":"Oxid. Med. Cell. Longev."},{"key":"2020072105163843000_ref22","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1111\/j.1471-4159.2005.03515.x","article-title":"3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington\u2019s disease","volume":"95","author":"Brouillet","year":"2005","journal-title":"J. Neurochem."},{"key":"2020072105163843000_ref23","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/ana.410390317","article-title":"Mitochondrial defect in Huntington\u2019s disease caudate nucleus","volume":"39","author":"Gu","year":"1996","journal-title":"Ann. Neurol."},{"key":"2020072105163843000_ref24","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1097\/NEN.0000000000000197","article-title":"Abnormalities in the tricarboxylic acid cycle in Huntington disease and in a Huntington disease mouse model","volume":"74","author":"Naseri","year":"2015","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"2020072105163843000_ref25","doi-asserted-by":"crossref","first-page":"4862","DOI":"10.1093\/hmg\/ddv209","article-title":"Oxidative metabolism in YAC128 mouse model of Huntington\u2019s disease","volume":"24","author":"Hamilton","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"2020072105163843000_ref26","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.4161\/cc.20423","article-title":"Huntingtin protein interactions altered by polyglutamine expansion as determined by quantitative proteomic analysis","volume":"11","author":"Ratovitski","year":"2012","journal-title":"Cell Cycle"},{"key":"2020072105163843000_ref27","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1523\/JNEUROSCI.0106-08.2008","article-title":"N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking","volume":"28","author":"Orr","year":"2008","journal-title":"J. Neurosci."},{"key":"2020072105163843000_ref28","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/nm.2313","article-title":"Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity","volume":"17","author":"Song","year":"2011","journal-title":"Nat. Med."},{"key":"2020072105163843000_ref29","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ydbio.2014.04.005","article-title":"Huntingtin protein is essential for mitochondrial metabolism, bioenergetics and structure in murine embryonic stem cells","volume":"391","author":"Ismailoglu","year":"2014","journal-title":"Dev. Biol."},{"key":"2020072105163843000_ref30","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.freeradbiomed.2013.04.016","article-title":"PGC-1\u03b1, mitochondrial dysfunction, and Huntington\u2019s disease","volume":"62","author":"Johri","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"2020072105163843000_ref31","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3233\/JHD-170264","article-title":"Towards an understanding of energy impairment in Huntington\u2019s disease brain","volume":"6","author":"Dubinsky","year":"2017","journal-title":"J. Huntingtons. Dis."},{"key":"2020072105163843000_ref32","first-page":"2762","article-title":"Oxidative metabolism and Ca2+ handling in isolated brain mitochondria and striatal neurons from R6\/2 mice, a model of Huntington\u2019s disease","volume":"25","author":"Hamilton","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"2020072105163843000_ref33","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1371\/journal.pgen.0030135","article-title":"Unbiased gene expression analysis implicates the huntingtin polyglutamine tract in extra-mitochondrial energy metabolism","volume":"3","author":"Lee","year":"2007","journal-title":"PLoS Genet."},{"key":"2020072105163843000_ref34","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.mad.2016.09.003","article-title":"The chicken or the egg: mitochondrial dysfunction as a cause or consequence of toxicity in Huntington\u2019s disease","volume":"161","author":"Polyzos","year":"2017","journal-title":"Mech. Ageing Dev."},{"key":"2020072105163843000_ref35","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1073\/pnas.0609833104","article-title":"Selective defect of in vivo glycolysis in early Huntington\u2019s disease striatum","volume":"104","author":"Powers","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2020072105163843000_ref36","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/ana.410410206","article-title":"Energy metabolism defects in Huntington\u2019s disease and effects of coenzyme Q10","volume":"41","author":"Koroshetz","year":"2004","journal-title":"Ann. Neurol."},{"key":"2020072105163843000_ref37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0081528","article-title":"Early deficits in glycolysis are specific to striatal neurons from a rat model of Huntington disease","volume":"8","author":"Gouarn\u00e9","year":"2013","journal-title":"PLoS One"},{"key":"2020072105163843000_ref38","first-page":"2813","article-title":"Oxygen consumption deficit in Huntington disease mouse brain under metabolic stress","volume":"25","author":"Lou","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"2020072105163843000_ref39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep34755","article-title":"The phasor-FLIM fingerprints reveal shifts from OXPHOS to enhanced glycolysis in Huntington disease","volume":"6","author":"Sameni","year":"2016","journal-title":"Sci. Rep."},{"key":"2020072105163843000_ref40","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.stem.2012.04.027","article-title":"Induced pluripotent stem cells from patients with Huntington\u2019s disease show CAG-repeat-expansion-associated phenotypes","volume":"11","year":"2012","journal-title":"Cell Stem Cell"},{"key":"2020072105163843000_ref41","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1093\/hmg\/ddv080","article-title":"HD iPSC-derived neural progenitors accumulate in culture and are susceptible to BDNF withdrawal due to glutamate toxicity","volume":"24","author":"Mattis","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"2020072105163843000_ref42","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/nn.4532","article-title":"Developmental alterations in Huntington\u2019s disease neural cells and pharmacological rescue in cells and mice","volume":"20","author":"The HD iPSC Consortium","year":"2017","journal-title":"Nat. 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Biol."},{"key":"2020072105163843000_ref47","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1186\/1471-2105-9-405","article-title":"iRefIndex: a consolidated protein interaction database with provenance","volume":"9","author":"Razick","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2020072105163843000_ref48","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neuron.2012.05.024","article-title":"Network organization of the huntingtin proteomic interactome in mammalian brain","volume":"75","author":"Shirasaki","year":"2012","journal-title":"Neuron"},{"key":"2020072105163843000_ref49","doi-asserted-by":"crossref","first-page":"D488","DOI":"10.1093\/nar\/gkv1024","article-title":"WikiPathways: capturing the full diversity of pathway knowledge","volume":"44","author":"Kutmon","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2020072105163843000_ref50","doi-asserted-by":"crossref","first-page":"14186","DOI":"10.1074\/jbc.M700827200","article-title":"Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain","volume":"282","author":"Castello","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2020072105163843000_ref51","doi-asserted-by":"crossref","first-page":"23357","DOI":"10.1074\/jbc.M100320200","article-title":"Modulation of mitochondrial function by hydrogen peroxide","volume":"276","author":"Nulton-Persson","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2020072105163843000_ref52","doi-asserted-by":"crossref","first-page":"e0160384","DOI":"10.1371\/journal.pone.0160384","article-title":"Novel metabolic abnormalities in the tricarboxylic acid cycle in peripheral cells from Huntington\u2019s disease patients","volume":"11","author":"Naseri","year":"2016","journal-title":"PLoS One"},{"key":"2020072105163843000_ref53","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1016\/j.celrep.2018.04.052","article-title":"Integrative characterization of the R6\/2 mouse model of Huntington\u2019s disease reveals dysfunctional astrocyte metabolism","volume":"23","author":"Skotte","year":"2018","journal-title":"Cell Rep."},{"key":"2020072105163843000_ref54","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1111\/j.1471-4159.1981.tb04687.x","article-title":"Brain levels of neuron-specific and nonneuronal enolase in Huntington\u2019s disease","volume":"37","author":"Marangos","year":"1981","journal-title":"J. Neurochem."},{"key":"2020072105163843000_ref55","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1016\/j.neurobiolaging.2013.11.025","article-title":"Superoxide dismutase 1 mutation in a cellular model of amyotrophic lateral sclerosis shifts energy generation from oxidative phosphorylation to glycolysis","volume":"35","author":"Allen","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"2020072105163843000_ref56","doi-asserted-by":"crossref","first-page":"141ra90","DOI":"10.1126\/scitranslmed.3003985","article-title":"Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson\u2019s disease","volume":"4","author":"Cooper","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"2020072105163843000_ref57","doi-asserted-by":"crossref","first-page":"E762","DOI":"10.1073\/pnas.1715865115","article-title":"Faulty neuronal determination and cell polarization are reverted by modulating HD early phenotypes","volume":"115","author":"Conforti","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2020072105163843000_ref58","doi-asserted-by":"crossref","first-page":"5736","DOI":"10.1073\/pnas.1603871113","article-title":"Selective expression of mutant huntingtin during development recapitulates characteristic features of Huntington\u2019s disease","volume":"113","author":"Molero","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2020072105163843000_ref59","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cmet.2013.11.020","article-title":"Aerobic glycolysis in the human brain is associated with development and neotenous gene expression","volume":"19","author":"Goyal","year":"2014","journal-title":"Cell Metab."},{"key":"2020072105163843000_ref60","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: cell proliferation","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Science"},{"key":"2020072105163843000_ref61","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.cmet.2017.07.010","article-title":"Loss of brain aerobic glycolysis in normal human aging","volume":"26","author":"Goyal","year":"2017","journal-title":"Cell Metab."},{"key":"2020072105163843000_ref62","doi-asserted-by":"crossref","first-page":"17763","DOI":"10.1073\/pnas.1010461107","article-title":"Spatial correlation between brain aerobic glycolysis and amyloid-\u03b2 (A\u03b2) deposition","volume":"107","author":"Vlassenko","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2020072105163843000_ref63","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.neurobiolaging.2018.03.014","article-title":"Aerobic glycolysis and tau deposition in preclinical Alzheimer\u2019s disease","volume":"67","author":"Vlassenko","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"2020072105163843000_ref64","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1074\/jbc.M111.309849","article-title":"Early alterations of brain cellular energy homeostasis in huntington disease models","volume":"287","author":"Mochel","year":"2012","journal-title":"J. Biol. Chem."},{"key":"2020072105163843000_ref65","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1212\/WNL.0000000000001214","article-title":"Triheptanoin improves brain energy metabolism in patients with Huntington disease","volume":"84","author":"Adanyeguh","year":"2015","journal-title":"Neurology"},{"key":"2020072105163843000_ref66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep15213","article-title":"Cytoplasmic sphingosine-1-phosphate pathway modulates neuronal autophagy","volume":"5","author":"Moruno Manchon","year":"2015","journal-title":"Sci. Rep."},{"key":"2020072105163843000_ref67","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41467-017-00353-6","article-title":"Identifying therapeutic targets by combining transcriptional data with ordinal clinical measurements","volume":"8","author":"Pirhaji","year":"2017","journal-title":"Nat. Commun."},{"key":"2020072105163843000_ref68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms3917","article-title":"A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington\u2019s disease in mice","volume":"4","author":"Acu\u00f1a","year":"2013","journal-title":"Nat. Commun."},{"key":"2020072105163843000_ref69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0134465","article-title":"HdhQ111 mice exhibit tissue specific metabolite profiles that include striatal lipid accumulation","volume":"10","author":"Carroll","year":"2015","journal-title":"PLoS One"},{"key":"2020072105163843000_ref70","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.cell.2006.09.015","article-title":"Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration","volume":"127","author":"Cui","year":"2006","journal-title":"Cell"},{"key":"2020072105163843000_ref71","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.cmet.2006.10.004","article-title":"Thermoregulatory and metabolic defects in Huntington\u2019s disease transgenic mice implicate PGC-1alpha in Huntington\u2019s disease neurodegeneration","volume":"4","author":"Weydt","year":"2006","journal-title":"Cell Metab."},{"key":"2020072105163843000_ref72","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.bbamcr.2017.01.009","article-title":"The UPR reduces glucose metabolism via IRE1 signaling","volume":"1864","author":"Harg","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"2020072105163843000_ref73","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.cell.2012.12.029","article-title":"Vesicular glycolysis provides on-board energy for fast axonal transport","volume":"152","author":"Zala","year":"2013","journal-title":"Cell"},{"key":"2020072105163843000_ref74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.03342","article-title":"Quantitative determinants of aerobic glycolysis identify flux through the enzyme GAPDH as a limiting step","volume":"3","author":"Shestov","year":"2014","journal-title":"Elife"},{"key":"2020072105163843000_ref75","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1126\/science.1224709","article-title":"Mitochondrial dynamics and apoptosis\u2014the ER connection","volume":"337","author":"Hoppins","year":"2012","journal-title":"Science"},{"key":"2020072105163843000_ref76","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.molcel.2016.01.031","article-title":"The emerging network of mitochondria-organelle contacts","volume":"61","author":"Murley","year":"2016","journal-title":"Mol. Cell"},{"key":"2020072105163843000_ref77","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1007\/s10517-017-3968-7","article-title":"Neuroprotective effect of \u03c31-receptors on the cell model of Huntington\u2019s disease","volume":"164","author":"Bol\u2019shakova","year":"2017","journal-title":"Bull. Exp. Biol. Med."},{"key":"2020072105163843000_ref78","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.nbd.2016.10.006","article-title":"The sigma-1 receptor mediates the beneficial effects of pridopidine in a mouse model of Huntington disease","volume":"97","author":"Ryskamp","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"2020072105163843000_ref79","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1016\/j.bbagen.2014.08.012","article-title":"Methyl pyruvate rescues mitochondrial damage caused by SIGMAR1 mutation related to amyotrophic lateral sclerosis","volume":"1840","author":"Tagashira","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"2020072105163843000_ref80","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.1523\/JNEUROSCI.2006-14.2016","article-title":"Histone deacetylase inhibitors protect against pyruvate dehydrogenase dysfunction in Huntington\u2019s disease","volume":"37","author":"Naia","year":"2017","journal-title":"J. Neurosci."},{"key":"2020072105163843000_ref81","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.freeradbiomed.2013.07.007","article-title":"SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury","volume":"65","author":"Yang","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"2020072105163843000_ref82","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nm.2558","article-title":"Neuroprotective role of Sirt1 in mammalian models of Huntington\u2019s disease through activation of multiple Sirt1 targets","volume":"18","author":"Jiang","year":"2012","journal-title":"Nat. Med."},{"key":"2020072105163843000_ref83","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.neuron.2014.12.019","article-title":"Reinstating aberrant mTORC1 activity in Huntington\u2019s disease mice improves disease phenotypes","volume":"85","author":"Lee","year":"2015","journal-title":"Neuron"},{"key":"2020072105163843000_ref84","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1016\/j.bmcl.2015.05.045","article-title":"Design and synthesis of silicon-containing fatty acid amide derivatives as novel peroxisome proliferator-activated receptor (PPAR) agonists","volume":"25","author":"Kajita","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2020072105163843000_ref85","doi-asserted-by":"crossref","first-page":"e30406","DOI":"10.1371\/journal.pone.0030406","article-title":"Metabolic state determines sensitivity to cellular stress in Huntington disease: normalization by activation of PPAR\u03b3","volume":"7","author":"Jin","year":"2012","journal-title":"PLoS One"},{"key":"2020072105163843000_ref86","doi-asserted-by":"crossref","first-page":"e00129","DOI":"10.1042\/AN20130030","article-title":"PPAR agonists as therapeutics for CNS trauma and neurological diseases","volume":"5","author":"Mandrekar-Colucci","year":"2013","journal-title":"ASN Neuro"},{"key":"2020072105163843000_ref87","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1126\/scitranslmed.aal2332","article-title":"PPAR\u03b4 activation by bexarotene promotes neuroprotection by restoring bioenergetic and quality control homeostasis","volume":"9","author":"Dickey","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"2020072105163843000_ref88","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1097\/ACO.0b013e3282f63c2e","article-title":"Ethyl pyruvate","volume":"21","author":"Fink","year":"2008","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"2020072105163843000_ref89","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1126\/scitranslmed.aag2210","article-title":"Mitochondrial pyruvate carrier regulates autophagy, inflammation, and neurodegeneration in experimental models of Parkinson\u2019s disease","volume":"8","author":"Ghosh","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"2020072105163843000_ref90","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1007\/s00018-013-1539-2","article-title":"Regulation of pyruvate metabolism and human disease","volume":"71","author":"Gray","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"2020072105163843000_ref91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fnins.2015.00017","article-title":"A unique array of neuroprotective effects of pyruvate in neuropathology","volume":"9","author":"Zilberter","year":"2015","journal-title":"Front. Neurosci."},{"key":"2020072105163843000_ref92","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Wisniewski","year":"2009","journal-title":"Nat. Methods"},{"key":"2020072105163843000_ref93","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1021\/pr300624g","article-title":"Statistical inference from multiple iTRAQ experiments without using common reference standards","volume":"12","author":"Herbrich","year":"2013","journal-title":"J. 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