{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:52:02Z","timestamp":1790650322865,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009991","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000}}],"reference-count":88,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-16-CE16-0021-01"],"award-info":[{"award-number":["ANR-16-CE16-0021-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-14-JPCD-0003-01"],"award-info":[{"award-number":["ANR-14-JPCD-0003-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006510","name":"Association pour la Recherche sur la Scl\u00e9rose Lat\u00e9rale Amyotrophique et autres Maladies du Motoneurone","doi-asserted-by":"publisher","award":["J19D08DOC026"],"award-info":[{"award-number":["J19D08DOC026"]}],"id":[{"id":"10.13039\/501100006510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Corruption of cellular prion protein (PrP<jats:sup>C<\/jats:sup>) function(s) at the plasma membrane of neurons is at the root of prion diseases, such as Creutzfeldt-Jakob disease and its variant in humans, and Bovine Spongiform Encephalopathies, better known as mad cow disease, in cattle. The roles exerted by PrP<jats:sup>C<\/jats:sup>, however, remain poorly elucidated. With the perspective to grasp the molecular pathways of neurodegeneration occurring in prion diseases, and to identify therapeutic targets, achieving a better understanding of PrP<jats:sup>C<\/jats:sup> roles is a priority. Based on global approaches that compare the proteome and metabolome of the PrP<jats:sup>C<\/jats:sup> expressing 1C11 neuronal stem cell line to those of PrP<jats:sup>null<\/jats:sup>-1C11 cells stably repressed for PrP<jats:sup>C<\/jats:sup> expression, we here unravel that PrP<jats:sup>C<\/jats:sup> contributes to the regulation of the energetic metabolism by orienting cells towards mitochondrial oxidative degradation of glucose. Through its coupling to cAMP\/protein kinase A signaling, PrP<jats:sup>C<\/jats:sup> tones down the expression of the pyruvate dehydrogenase kinase 4 (PDK4). Such an event favors the transfer of pyruvate into mitochondria and its conversion into acetyl-CoA by the pyruvate dehydrogenase complex and, thereby, limits fatty acids \u03b2-oxidation and subsequent onset of oxidative stress conditions. The corruption of PrP<jats:sup>C<\/jats:sup> metabolic role by pathogenic prions PrP<jats:sup>Sc<\/jats:sup> causes in the mouse hippocampus an imbalance between glucose oxidative degradation and fatty acids \u03b2-oxidation in a PDK4-dependent manner. The inhibition of PDK4 extends the survival of prion-infected mice, supporting that PrP<jats:sup>Sc<\/jats:sup>-induced deregulation of PDK4 activity and subsequent metabolic derangements contribute to prion diseases. Our study posits PDK4 as a potential therapeutic target to fight against prion diseases.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009991","type":"journal-article","created":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T04:52:16Z","timestamp":1633495936000},"page":"e1009991","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Loss of prion protein control of glucose metabolism promotes neurodegeneration in model of prion diseases"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7750-5803","authenticated-orcid":true,"given":"H\u00e9l\u00e8ne","family":"Arnould","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Baudouin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Baudry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5525-0571","authenticated-orcid":true,"given":"Luiz W.","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Ardila-Osorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Math\u00e9a","family":"Pietri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5958-9732","authenticated-orcid":true,"given":"C\u00e9dric","family":"Caradeuc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7383-4132","authenticated-orcid":true,"given":"Cynthia","family":"Soultawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6754-1624","authenticated-orcid":true,"given":"Declan","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2809-9439","authenticated-orcid":true,"given":"Marjorie","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Crozet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0350-0935","authenticated-orcid":true,"given":"Fatima","family":"Djouadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille","family":"Laforge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4929-763X","authenticated-orcid":true,"given":"Gildas","family":"Bertho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Kellermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4809-1020","authenticated-orcid":true,"given":"Jean-Marie","family":"Launay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6962-0919","authenticated-orcid":true,"given":"Gerold","family":"Schmitt-Ulms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1377-2670","authenticated-orcid":true,"given":"Benoit","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"ppat.1009991.ref001","doi-asserted-by":"crossref","first-page":"13363","DOI":"10.1073\/pnas.95.23.13363","volume":"95","author":"SB Prusiner","year":"1998","journal-title":"Prions. Proc Natl Acad Sci U S A"},{"key":"ppat.1009991.ref002","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/nature07761","article-title":"Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers","volume":"457","author":"J Laur\u00e9n","year":"2009","journal-title":"Nature"},{"key":"ppat.1009991.ref003","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1038\/nm.3302","article-title":"PDK1 decreases TACE-mediated \u03b1-secretase activity and promotes disease progression in prion and Alzheimer\u2019s diseases","volume":"19","author":"M Pietri","year":"2013","journal-title":"Nat Med"},{"key":"ppat.1009991.ref004","doi-asserted-by":"crossref","first-page":"10050","DOI":"10.1038\/s41598-017-10236-x","article-title":"\u03b1-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication","volume":"7","author":"S Auli\u0107","year":"2017","journal-title":"Sci Rep"},{"key":"ppat.1009991.ref005","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1080\/19336896.2017.1334748","article-title":"The cellular prion protein (PrPC) as neuronal receptor for \u03b1-synuclein","volume":"11","author":"L Urrea","year":"2017","journal-title":"Prion"},{"key":"ppat.1009991.ref006","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.neuron.2006.04.020","article-title":"New insights into prion structure and toxicity","volume":"50","author":"DA Harris","year":"2006","journal-title":"Neuron"},{"key":"ppat.1009991.ref007","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1038\/nn.3178","article-title":"Alzheimer amyloid-\u03b2 oligomer bound to postsynaptic prion protein activates Fyn to impair neurons","volume":"15","author":"JW Um","year":"2012","journal-title":"Nat Neurosci"},{"key":"ppat.1009991.ref008","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1038\/nn.4648","article-title":"\u03b1-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B","volume":"20","author":"DG Ferreira","year":"2017","journal-title":"Nat Neurosci"},{"key":"ppat.1009991.ref009","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1038\/emboj.2011.86","article-title":"The cellular prion protein mediates neurotoxic signalling of \u03b2-sheet-rich conformers independent of prion replication","volume":"30","author":"UK Resenberger","year":"2011","journal-title":"EMBO J"},{"key":"ppat.1009991.ref010","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/01616412.2016.1251711","article-title":"Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders","volume":"39","author":"MT Islam","year":"2017","journal-title":"Neurol Res"},{"key":"ppat.1009991.ref011","first-page":"131","article-title":"ER Stress and Neurodegenerative Disease: A Cause or Effect Relationship?","volume":"414","author":"F Cabral-Miranda","year":"2018","journal-title":"Curr Top Microbiol Immunol"},{"key":"ppat.1009991.ref012","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nrd.2018.109","article-title":"Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing","volume":"17","author":"B Boland","year":"2018","journal-title":"Nat Rev Drug Discov"},{"key":"ppat.1009991.ref013","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.vetmic.2019.04.026","article-title":"Autophagy impairment in highly prion-affected brain areas of sheep experimentally infected with atypical scrapie","volume":"233","author":"\u00d3 L\u00f3pez-P\u00e9rez","year":"2019","journal-title":"Vet Microbiol"},{"key":"ppat.1009991.ref014","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1042\/BST20180025","article-title":"Mitochondrial dysfunction and neurodegenerative proteinopathies: mechanisms and prospects for therapeutic intervention","volume":"46","author":"T Briston","year":"2018","journal-title":"Biochem Soc Trans"},{"key":"ppat.1009991.ref015","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1038\/s41418-018-0148-x","article-title":"Alterations in neuronal metabolism contribute to the pathogenesis of prion disease","volume":"25","author":"J-M Bourgognon","year":"2018","journal-title":"Cell Death Differ"},{"key":"ppat.1009991.ref016","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.neuron.2008.10.010","article-title":"Mitochondria in neuroplasticity and neurological disorders","volume":"60","author":"MP Mattson","year":"2008","journal-title":"Neuron"},{"key":"ppat.1009991.ref017","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1016\/j.metabol.2016.05.018","article-title":"Role of metabolism in neurodegenerative disorders","volume":"65","author":"C Procaccini","year":"2016","journal-title":"Metabolism"},{"key":"ppat.1009991.ref018","doi-asserted-by":"crossref","first-page":"e12924","DOI":"10.1111\/acel.12924","article-title":"Systems biology identifies preserved integrity but impaired metabolism of mitochondria due to a glycolytic defect in Alzheimer\u2019s disease neurons","volume":"18","author":"P Theurey","year":"2019","journal-title":"Aging Cell"},{"key":"ppat.1009991.ref019","doi-asserted-by":"crossref","first-page":"336","DOI":"10.3389\/fnagi.2018.00336","article-title":"Modulation of Mitochondrial Dynamics in Neurodegenerative Diseases: An Insight Into Prion Diseases","volume":"10","author":"T Zhu","year":"2018","journal-title":"Front Aging Neurosci"},{"key":"ppat.1009991.ref020","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.15252\/embj.201695810","article-title":"Brain metabolism in health, aging, and neurodegeneration","volume":"36","author":"S Camandola","year":"2017","journal-title":"EMBO J"},{"key":"ppat.1009991.ref021","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s12035-013-8529-0","article-title":"Gene expression resulting from PrPC ablation and PrPC overexpression in murine and cellular models","volume":"49","author":"F Llorens","year":"2014","journal-title":"Mol Neurobiol"},{"key":"ppat.1009991.ref022","doi-asserted-by":"crossref","first-page":"589","DOI":"10.2174\/138955706776876159","article-title":"Recent advances in clarifying prion protein functions using knockout mice and derived cell lines","volume":"6","author":"A Sakudo","year":"2006","journal-title":"Mini Rev Med Chem"},{"key":"ppat.1009991.ref023","doi-asserted-by":"crossref","first-page":"83","DOI":"10.4161\/pri.1.2.4346","article-title":"The prion protein knockout mouse: a phenotype under challenge","volume":"1","author":"AD Steele","year":"2007","journal-title":"Prion."},{"key":"ppat.1009991.ref024","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/bmb\/66.1.43","article-title":"PrP knock-out and PrP transgenic mice in prion research","volume":"66","author":"C Weissmann","year":"2003","journal-title":"Br Med Bull"},{"key":"ppat.1009991.ref025","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1084\/jem.20151610","article-title":"Strictly co-isogenic C57BL\/6J-Prnp-\/- mice: A rigorous resource for prion science","volume":"213","author":"M Nuvolone","year":"2016","journal-title":"J Exp Med"},{"key":"ppat.1009991.ref026","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1186\/1471-2164-11-448","article-title":"Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse","volume":"11","author":"S Chadi","year":"2010","journal-title":"BMC Genomics"},{"key":"ppat.1009991.ref027","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1152\/physrev.00007.2007","article-title":"Physiology of the prion protein","volume":"88","author":"R Linden","year":"2008","journal-title":"Physiol Rev"},{"key":"ppat.1009991.ref028","doi-asserted-by":"crossref","first-page":"9186","DOI":"10.1074\/jbc.275.13.9186","article-title":"Regulation by neurotransmitter receptors of serotonergic or catecholaminergic neuronal cell differentiation","volume":"275","author":"S Mouillet-Richard","year":"2000","journal-title":"J Biol Chem"},{"key":"ppat.1009991.ref029","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1126\/science.289.5486.1925","article-title":"Signal transduction through prion protein","volume":"289","author":"S Mouillet-Richard","year":"2000","journal-title":"Science"},{"key":"ppat.1009991.ref030","doi-asserted-by":"crossref","first-page":"e2668","DOI":"10.1038\/cddis.2017.37","article-title":"Regulation of RhoA activity by the cellular prion protein","volume":"8","author":"H-J Kim","year":"2017","journal-title":"Cell Death Dis"},{"key":"ppat.1009991.ref031","first-page":"678","article-title":"Neuritogenesis: the prion protein controls \u03b21 integrin signaling activity","volume":"26","author":"D Loubet","year":"2012","journal-title":"FASEB J Off Publ Fed Am Soc Exp Biol"},{"key":"ppat.1009991.ref032","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.neulet.2012.10.032","article-title":"Atorvastatin stimulates neuroblastoma cells to induce neurite outgrowth by increasing cellular prion protein expression","volume":"531","author":"T Watanabe","year":"2012","journal-title":"Neurosci Lett"},{"key":"ppat.1009991.ref033","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1091\/mbc.e11-12-1006","article-title":"Reggies\/flotillins regulate E-cadherin-mediated cell contact formation by affecting EGFR trafficking","volume":"23","author":"GP Solis","year":"2012","journal-title":"Mol Biol Cell"},{"key":"ppat.1009991.ref034","doi-asserted-by":"crossref","first-page":"304","DOI":"10.2174\/156652412799218912","article-title":"Cellular prion and its catabolites in the brain: production and function","volume":"12","author":"M-V Guillot-Sestier","year":"2012","journal-title":"Curr Mol Med"},{"key":"ppat.1009991.ref035","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1093\/emboj\/cdf325","article-title":"Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection","volume":"21","author":"SM Zanata","year":"2002","journal-title":"EMBO J"},{"key":"ppat.1009991.ref036","doi-asserted-by":"crossref","first-page":"13326","DOI":"10.1073\/pnas.2235648100","article-title":"NADPH oxidase and extracellular regulated kinases 1\/2 are targets of prion protein signaling in neuronal and nonneuronal cells","volume":"100","author":"B Schneider","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1009991.ref037","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1111\/j.1471-4159.2009.06176.x","article-title":"Cellular prion protein coupling to TACE-dependent TNF-alpha shedding controls neurotransmitter catabolism in neuronal cells","volume":"110","author":"E Pradines","year":"2009","journal-title":"J Neurochem"},{"key":"ppat.1009991.ref038","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/jnr.21506","article-title":"Protective effect of prion protein via the N-terminal region in mediating a protective effect on paraquat-induced oxidative injury in neuronal cells","volume":"86","author":"I Dupiereux","year":"2008","journal-title":"J Neurosci Res"},{"key":"ppat.1009991.ref039","doi-asserted-by":"crossref","first-page":"7671","DOI":"10.1038\/s41598-017-08110-x","article-title":"Protective role of cellular prion protein against TNF\u03b1-mediated inflammation through TACE \u03b1-secretase","volume":"7","author":"J Ezpeleta","year":"2017","journal-title":"Sci Rep"},{"key":"ppat.1009991.ref040","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1089\/ars.2014.6032","article-title":"Prion protein and copper cooperatively protect neurons by modulating NMDA receptor through S-nitrosylation","volume":"22","author":"L Gasperini","year":"2015","journal-title":"Antioxid Redox Signal"},{"key":"ppat.1009991.ref041","doi-asserted-by":"crossref","first-page":"8654","DOI":"10.1038\/s41598-018-26685-x","article-title":"The prion protein is embedded in a molecular environment that modulates transforming growth factor \u03b2 and integrin signaling","volume":"8","author":"F Ghodrati","year":"2018","journal-title":"Sci Rep"},{"key":"ppat.1009991.ref042","doi-asserted-by":"crossref","first-page":"21857","DOI":"10.1074\/jbc.M116.743435","article-title":"The N Terminus of the Prion Protein Mediates Functional Interactions with the Neuronal Cell Adhesion Molecule (NCAM) Fibronectin Domain","volume":"291","author":"U Slap\u0161ak","year":"2016","journal-title":"J Biol Chem"},{"key":"ppat.1009991.ref043","doi-asserted-by":"crossref","DOI":"10.1177\/1759091416679074","article-title":"NCAM1 Polysialylation: The Prion Protein\u2019s Elusive Reason for Being?","volume":"8","author":"M Mehrabian","year":"2016","journal-title":"ASN Neuro"},{"key":"ppat.1009991.ref044","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1523\/JNEUROSCI.4149-12.2013","article-title":"PrPC controls via protein kinase A the direction of synaptic plasticity in the immature hippocampus","volume":"33","author":"MD Caiati","year":"2013","journal-title":"J Neurosci Off J Soc Neurosci"},{"key":"ppat.1009991.ref045","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.1111\/j.1460-9568.2006.05156.x","article-title":"The interaction between prion protein and laminin modulates memory consolidation","volume":"24","author":"AS Coitinho","year":"2006","journal-title":"Eur J Neurosci"},{"key":"ppat.1009991.ref046","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.nbd.2007.01.005","article-title":"Short-term memory formation and long-term memory consolidation are enhanced by cellular prion association to stress-inducible protein 1","volume":"26","author":"AS Coitinho","year":"2007","journal-title":"Neurobiol Dis"},{"key":"ppat.1009991.ref047","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/nrn2285","article-title":"Polysialic acid in the plasticity of the developing and adult vertebrate nervous system","volume":"9","author":"U. Rutishauser","year":"2008","journal-title":"Nat Rev Neurosci."},{"key":"ppat.1009991.ref048","doi-asserted-by":"crossref","first-page":"e0156779","DOI":"10.1371\/journal.pone.0156779","article-title":"Prion Protein Deficiency Causes Diverse Proteome Shifts in Cell Models That Escape Detection in Brain Tissue","volume":"11","author":"M Mehrabian","year":"2016","journal-title":"PloS One"},{"key":"ppat.1009991.ref049","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/cem.695","article-title":"Orthogonal projections to latent structures (O-PLS)","volume":"16","author":"J Trygg","year":"2002","journal-title":"J Chemom"},{"key":"ppat.1009991.ref050","doi-asserted-by":"crossref","first-page":"E242","DOI":"10.1152\/ajpendo.90388.2008","article-title":"The facilitative glucose transporter GLUT3: 20 years of distinction","volume":"295","author":"IA Simpson","year":"2008","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ppat.1009991.ref051","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1042\/bj3580069","article-title":"Regulation of pyruvate dehydrogenase activity through phosphorylation at multiple sites","volume":"358","author":"E Kolobova","year":"2001","journal-title":"Biochem J"},{"key":"ppat.1009991.ref052","doi-asserted-by":"crossref","first-page":"E855","DOI":"10.1152\/ajpendo.00526.2002","article-title":"Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs","volume":"284","author":"MC Sugden","year":"2003","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ppat.1009991.ref053","doi-asserted-by":"crossref","first-page":"328","DOI":"10.4093\/dmj.2012.36.5.328","article-title":"Transcriptional regulation of pyruvate dehydrogenase kinase","volume":"36","author":"JY Jeong","year":"2012","journal-title":"Diabetes Metab J"},{"key":"ppat.1009991.ref054","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.biocel.2015.03.008","article-title":"Activation of OR1A1 suppresses PPAR-\u03b3 expression by inducing HES-1 in cultured hepatocytes","volume":"64","author":"C Wu","year":"2015","journal-title":"Int J Biochem Cell Biol"},{"key":"ppat.1009991.ref055","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1530\/EC-13-0049","article-title":"PKA regulatory subunit R2B is required for murine and human adipocyte differentiation","volume":"2","author":"E Peverelli","year":"2013","journal-title":"Endocr Connect"},{"key":"ppat.1009991.ref056","doi-asserted-by":"crossref","first-page":"8474","DOI":"10.1038\/s41598-017-09163-8","article-title":"Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts","volume":"7","author":"X Liu","year":"2017","journal-title":"Sci Rep"},{"key":"ppat.1009991.ref057","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1093\/emboj\/cdf324","article-title":"Cellular prion protein transduces neuroprotective signals","volume":"21","author":"LB Chiarini","year":"2002","journal-title":"EMBO J"},{"key":"ppat.1009991.ref058","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1042\/bj2140021","article-title":"Observations on the affinity for carnitine, and malonyl-CoA sensitivity, of carnitine palmitoyltransferase I in animal and human tissues. Demonstration of the presence of malonyl-CoA in non-hepatic tissues of the rat","volume":"214","author":"JD McGarry","year":"1983","journal-title":"Biochem J"},{"key":"ppat.1009991.ref059","doi-asserted-by":"crossref","first-page":"276","DOI":"10.2337\/diabetes.51.2.276","article-title":"Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin","volume":"51","author":"B Huang","year":"2002","journal-title":"Diabetes"},{"key":"ppat.1009991.ref060","first-page":"789","article-title":"Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice","volume":"118","author":"C Bonnard","year":"2008","journal-title":"J Clin Invest"},{"key":"ppat.1009991.ref061","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1006\/jmcc.1996.0077","article-title":"Regulation of fatty acid oxidation by acetyl-CoA generated from glucose utilization in isolated myocytes","volume":"28","author":"S Abdel-aleem","year":"1996","journal-title":"J Mol Cell Cardiol"},{"key":"ppat.1009991.ref062","doi-asserted-by":"crossref","first-page":"e1005073","DOI":"10.1371\/journal.ppat.1005073","article-title":"Double-Edge Sword of Sustained ROCK Activation in Prion Diseases through Neuritogenesis Defects and Prion Accumulation","volume":"11","author":"A Alleaume-Butaux","year":"2015","journal-title":"PLoS Pathog."},{"key":"ppat.1009991.ref063","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.1038\/s41467-019-11333-3","article-title":"Production of seedable Amyloid-\u03b2 peptides in model of prion diseases upon PrPSc-induced PDK1 overactivation","volume":"10","author":"J Ezpeleta","year":"2019","journal-title":"Nat Commun"},{"key":"ppat.1009991.ref064","doi-asserted-by":"crossref","first-page":"7104","DOI":"10.1128\/JVI.79.11.7104-7112.2005","article-title":"Biological and biochemical characteristics of prion strains conserved in persistently infected cell cultures","volume":"79","author":"K Arima","year":"2005","journal-title":"J Virol"},{"key":"ppat.1009991.ref065","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"MG Vander Heiden","year":"2009","journal-title":"Science"},{"key":"ppat.1009991.ref066","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1126\/science.124.3215.269","article-title":"On respiratory impairment in cancer cells","volume":"124","author":"O. Warburg","year":"1956","journal-title":"Science"},{"key":"ppat.1009991.ref067","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1042\/BST0340217","article-title":"Regulation of the pyruvate dehydrogenase complex","volume":"34","author":"MS Patel","year":"2006","journal-title":"Biochem Soc Trans"},{"key":"ppat.1009991.ref068","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1016\/j.cellsig.2008.07.016","article-title":"CREB-dependent gene regulation by prion protein: impact on MMP-9 and beta-dystroglycan","volume":"20","author":"E Pradines","year":"2008","journal-title":"Cell Signal"},{"key":"ppat.1009991.ref069","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/nature02110","article-title":"CREB controls hepatic lipid metabolism through nuclear hormone receptor PPAR-gamma","volume":"426","author":"S Herzig","year":"2003","journal-title":"Nature"},{"key":"ppat.1009991.ref070","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20184640","article-title":"The Link of the Prion Protein with Ca2+ Metabolism and ROS Production, and the Possible Implication in A\u03b2 Toxicity","volume":"20","author":"A De Mario","year":"2019","journal-title":"Int J Mol Sci"},{"key":"ppat.1009991.ref071","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1038\/emboj.2008.122","article-title":"Stress-protective signalling of prion protein is corrupted by scrapie prions","volume":"27","author":"AS Rambold","year":"2008","journal-title":"EMBO J"},{"key":"ppat.1009991.ref072","doi-asserted-by":"crossref","first-page":"2105607","DOI":"10.1155\/2019\/2105607","article-title":"Oxidative Stress in Neurodegenerative Diseases: From a Mitochondrial Point of View","volume":"2019","author":"G Cenini","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"ppat.1009991.ref073","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/1873-3468.12964","article-title":"Role of mitochondrial ROS in the brain: from physiology to neurodegeneration","volume":"592","author":"PR Angelova","year":"2018","journal-title":"FEBS Lett"},{"key":"ppat.1009991.ref074","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.tem.2016.12.003","article-title":"Peroxisomal Dysfunction in Age-Related Diseases","volume":"28","author":"CM Cipolla","year":"2017","journal-title":"Trends Endocrinol Metab TEM"},{"key":"ppat.1009991.ref075","doi-asserted-by":"crossref","first-page":"e456","DOI":"10.1038\/cddis.2012.195","article-title":"Pathogenic prions deviate PrP(C) signaling in neuronal cells and impair A-beta clearance","volume":"4","author":"E Pradines","year":"2013","journal-title":"Cell Death Dis"},{"key":"ppat.1009991.ref076","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1038\/sj.bjc.6604554","article-title":"Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer","volume":"99","author":"ED Michelakis","year":"2008","journal-title":"Br J Cancer"},{"key":"ppat.1009991.ref077","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.pharmthera.2016.10.018","article-title":"Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1","volume":"170","author":"MO James","year":"2017","journal-title":"Pharmacol Ther"},{"key":"ppat.1009991.ref078","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/j.1471-4159.2009.06123.x","article-title":"PrPc activation induces neurite outgrowth and differentiation in PC12 cells: role for caveolin-1 in the signal transduction pathway","volume":"110","author":"B Pantera","year":"2009","journal-title":"J Neurochem"},{"key":"ppat.1009991.ref079","doi-asserted-by":"crossref","first-page":"e114594","DOI":"10.1371\/journal.pone.0114594","article-title":"CRISPR-Cas9-based knockout of the prion protein and its effect on the proteome","volume":"9","author":"M Mehrabian","year":"2014","journal-title":"PloS One"},{"key":"ppat.1009991.ref080","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1021\/ac403837r","article-title":"Urinary metabolic fingerprint of acute intermittent porphyria analyzed by (1)H NMR spectroscopy","volume":"86","author":"M Carichon","year":"2014","journal-title":"Anal Chem"},{"key":"ppat.1009991.ref081","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/cem.1187","article-title":"CV-ANOVA for significance testing of PLS and OPLS models","volume":"22","author":"L Eriksson","year":"2008","journal-title":"J Chemom"},{"key":"ppat.1009991.ref082","doi-asserted-by":"crossref","first-page":"W652","DOI":"10.1093\/nar\/gkp356","article-title":"MetaboAnalyst: a web server for metabolomic data analysis and interpretation","volume":"37","author":"J Xia","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"ppat.1009991.ref083","doi-asserted-by":"crossref","first-page":"W486","DOI":"10.1093\/nar\/gky310","article-title":"MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis","volume":"46","author":"J Chong","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"ppat.1009991.ref084","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1038\/nprot.2007.207","article-title":"Isolation and culture of adult neurons and neurospheres","volume":"2","author":"GJ Brewer","year":"2007","journal-title":"Nat Protoc"},{"key":"ppat.1009991.ref085","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/jnc.12026","article-title":"Microwave irradiation decreases ATP, increases free [Mg2+], and alters in vivo intracellular reactions in rat brain","volume":"123","author":"S Srivastava","year":"2012","journal-title":"J Neurochem"},{"key":"ppat.1009991.ref086","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1016\/j.neurobiolaging.2012.11.023","article-title":"A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer\u2019s disease","volume":"34","author":"Y Kashiwaya","year":"2013","journal-title":"Neurobiol Aging"},{"key":"ppat.1009991.ref087","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1177\/0271678X16659498","article-title":"Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function","volume":"37","author":"KN Tan","year":"2017","journal-title":"J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab"},{"key":"ppat.1009991.ref088","doi-asserted-by":"crossref","first-page":"6381","DOI":"10.1039\/C4AY00804A","article-title":"A new spectrophotometric assay for measuring pyruvate dehydrogenase complex activity: a comparative evaluation","volume":"6","author":"C-J Ke","year":"2014","journal-title":"Anal Methods"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1009991","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009991","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T18:54:46Z","timestamp":1634324086000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009991"}},"subtitle":[],"editor":[{"given":"Umberto","family":"Agrimi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,10,5]]},"references-count":88,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1009991","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1009991","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,5]]}}}