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HD usually manifests in mid-life with loss of GABAergic projection neurons from the striatum accompanied by progressive atrophy of the putamen followed by other brain regions, but linkages between the genetics and neurodegeneration are not understood. We measured metabolic perturbations in HD-human brain in a case-control study, identifying pervasive lowering of vitamin B5, the obligatory precursor of coenzyme A (CoA) that is essential for normal intermediary metabolism. Cerebral pantothenate deficiency is a newly-identified metabolic defect in human HD that could potentially: (i) impair neuronal CoA biosynthesis; (ii) stimulate polyol-pathway activity; (iii) impair glycolysis and tricarboxylic acid cycle activity; and (iv) modify brain-urea metabolism. Pantothenate deficiency could lead to neurodegeneration\/dementia in HD that might be preventable by treatment with vitamin B5.<\/jats:p>","DOI":"10.3390\/metabo9060113","type":"journal-article","created":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T10:55:44Z","timestamp":1560250544000},"page":"113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington\u2019s Disease"],"prefix":"10.3390","volume":"9","author":[{"given":"Stefano","family":"Patassini","sequence":"first","affiliation":[{"name":"Centre for Advanced Discovery and Experimental Therapeutics, Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine &amp; Health, The University of Manchester, Manchester M19 9NT, UK"},{"name":"School of Biological Sciences, Faculty of Science, University of Auckland, Auckland 1142, New Zealand"},{"name":"Owlstone Medical, Cambridge Science Park, Cambridge CB4 0GJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Begley","sequence":"additional","affiliation":[{"name":"Centre for Advanced Discovery and Experimental Therapeutics, Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine &amp; 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Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1056\/NEJM199405193302001","article-title":"A worldwide study of the Huntington\u2019s disease mutation: The sensitivity and specificity of measuring CAG repeats","volume":"330","author":"Andrew","year":"1994","journal-title":"New Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.neuron.2016.02.003","article-title":"The biology of huntingtin","volume":"89","author":"Soudou","year":"2016","journal-title":"Neuron"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1111\/ene.13107","article-title":"The societal cost of Huntington\u2019s disease: Are we underestimating the burden?","volume":"23","author":"Jones","year":"2016","journal-title":"Eur. J. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/B978-0-444-52014-2.00004-5","article-title":"Huntington\u2019s disease\u2014Neuropathology","volume":"Volume 100","author":"Weiner","year":"2011","journal-title":"Hyperkinetic Movement Disorders"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.bbadis.2016.06.002","article-title":"Metabolite mapping reveals severe widespread perturbation of multiple metabolic processes in Huntington\u2019s disease human brain","volume":"1862","author":"Patassini","year":"2016","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.bbadis.2016.03.001","article-title":"Graded perturbations of metabolism in multiple regions of human brain in Alzheimer\u2019s disease: Snapshot of a pervasive metabolic disorder","volume":"1862","author":"Xu","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/7854_2014_354","article-title":"The neuropathology of Huntington\u2019s disease","volume":"Volume 22","author":"Nguyen","year":"2014","journal-title":"Behavioral Neurobiology Of Huntington\u2019S Disease and Parkinson\u2019S Disease"},{"key":"ref_12","first-page":"215","article-title":"Brain white-matter volume loss and glucose hypometabolism precede the clinical symptoms of Huntington\u2019s disease","volume":"47","author":"Ciarmiello","year":"2006","journal-title":"J. Nucl. Med."},{"key":"ref_13","first-page":"1171","article-title":"Current status of PET imaging in Huntington\u2019s disease","volume":"43","author":"Pagano","year":"2016","journal-title":"Eur. J. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/S1474-4422(15)00177-5","article-title":"Treating the whole body in Huntington\u2019s disease","volume":"14","author":"Carroll","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4076","DOI":"10.1172\/JCI69411","article-title":"Metabolic network as a progression biomarker of premanifest Huntington\u2019s disease","volume":"123","author":"Tang","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jpba.2016.07.008","article-title":"Metabolomics studies in brain tissue: A review","volume":"130","author":"Garcia","year":"2016","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1373\/clinchem.2012.199257","article-title":"Preanalytical aspects and sample quality assessment in metabolomics studies of human blood","volume":"59","author":"Yin","year":"2013","journal-title":"Clin. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1515\/CCLM.2008.242","article-title":"Comprehensive profiling of the human circulating endocannabinoid metabolome: Clinical sampling and sample storage parameters","volume":"46","author":"Wood","year":"2008","journal-title":"Clin. Chem. Lab. Med. (CCLM)"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.bbrc.2015.10.140","article-title":"Identification of elevated urea as a severe, ubiquitous metabolic defect in the brain of patients with Huntington\u2019s disease","volume":"468","author":"Patassini","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"E11293","DOI":"10.1073\/pnas.1711243115","article-title":"Brain urea increase is an early Huntington\u2019s disease pathogenic event observed in a prodromal transgenic sheep model and HD cases","volume":"114","author":"Handley","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"46ps42","DOI":"10.1126\/scitranslmed.3001249","article-title":"Recommendations for biomarker identification and qualification in clinical proteomics","volume":"2","author":"Mischak","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/jnc.13092","article-title":"Major involvement of Na(+)-dependent multivitamin transporter (SLC5A6\/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells","volume":"134","author":"Uchida","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1042\/BST20140098","article-title":"Defective pantothenate metabolism and neurodegeneration","volume":"42","author":"Hayflick","year":"2014","journal-title":"Biochem. Soc. Trans."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1212\/WNL.58.11.1673","article-title":"HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration","volume":"58","author":"Ching","year":"2002","journal-title":"Neurology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1056\/NEJMoa020817","article-title":"Genetic, clinical, and radiographic delineation of Hallervorden\u2013Spatz syndrome","volume":"348","author":"Hayflick","year":"2003","journal-title":"New Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kennedy, D.O. (2016). B Vitamins and the brain: mechanisms, dose and efficacy\u2014A review. Nutrients, 8.","DOI":"10.3390\/nu8020068"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14802","DOI":"10.1073\/pnas.011597698","article-title":"The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes","volume":"98","author":"Zhou","year":"2001","journal-title":"Proc. Acad. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"21431","DOI":"10.1074\/jbc.M201708200","article-title":"Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics","volume":"277","author":"Daugherty","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1042\/BST20140106","article-title":"Alteration of the coenzyme A biosynthetic pathway in neurodegeneration with brain iron accumulation syndromes","volume":"42","author":"Venco","year":"2014","journal-title":"Biochem. Soc. Trans."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1016\/S0140-6736(05)67889-0","article-title":"Global prevalence of dementia: A Delphi consensus study","volume":"366","author":"Ferri","year":"2005","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/alzrt269","article-title":"Alzheimer\u2019s disease drug-development pipeline: Few candidates, frequent failures","volume":"6","author":"Cummings","year":"2014","journal-title":"Alzheimer\u2019s Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/nyas.13031","article-title":"Vitamin B1 (thiamine) and dementia","volume":"1367","author":"Gibson","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1136\/jnnp.2003.025858","article-title":"Dietary niacin and the risk of incident Alzheimer\u2019s disease and of cognitive decline","volume":"75","author":"Morris","year":"2004","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_34","first-page":"CD004514","article-title":"Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people","volume":"8","author":"Malouf","year":"2008","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1136\/bmj.324.7352.1512","article-title":"Folic acid, ageing, depression, and dementia","volume":"324","author":"Reynolds","year":"2002","journal-title":"Br. Med. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0021-9258(20)78929-5","article-title":"On the nature and role of the fatty acids essential in nutrition","volume":"86","author":"Burr","year":"1930","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1194\/jlr.R055095","article-title":"Discovery of essential fatty acids","volume":"56","author":"Spector","year":"2015","journal-title":"J. Lipid. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1093\/jn\/119.12.1880","article-title":"The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats","volume":"119","author":"Bourre","year":"1989","journal-title":"J. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"657","DOI":"10.3945\/ajcn.113.076349","article-title":"Effects of homocysteine lowering with B vitamins on cognitive aging: Meta-analysis of 11 trials with cognitive data on 22,000 individuals","volume":"100","author":"Clarke","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4103\/2229-4708.72226","article-title":"Bioanalytical method validation: An updated review","volume":"1","author":"Tiwari","year":"2010","journal-title":"Pharm. Methods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1007\/s00216-010-4139-0","article-title":"Towards an unbiased metabolic profiling of protozoan parasites: Optimisation of a Leishmania sampling protocol for HILIC-orbitrap analysis","volume":"398","author":"Jankevics","year":"2010","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_42","first-page":"101","article-title":"Reliability and reproducibility issues in DNA microarray measurements","volume":"22","author":"Draghici","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/0006-8993(74)90247-9","article-title":"Post-mortal changes of dopamine and homovanillic acid levels in rat striatum as measured by mass fragmentography","volume":"65","author":"Wiesel","year":"1974","journal-title":"Brain Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1471-4159.1977.tb03942.x","article-title":"Rapid post mortem changes in 3,4-dihydroxyphenylacetic acid (DOPAC), a dopamine metabolite, in rat striatum","volume":"29","author":"Moleman","year":"1977","journal-title":"J. Neurochem."},{"key":"ref_45","first-page":"143","article-title":"Post mortem stability of catecholamines in discrete regions of rat brain","volume":"23","author":"Roubein","year":"1979","journal-title":"Commun. Chem. Pathol. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1111\/j.1471-4159.1984.tb12746.x","article-title":"Postmortem and Regional Changes of Serotonin, 5-Hydroxyindoleacetic Acid, and Tryptophan in Brain","volume":"42","author":"McIntyre","year":"1984","journal-title":"J. Neurochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e31126","DOI":"10.7554\/eLife.31126","article-title":"Neuropathological and transcriptomic characteristics of the aged brain","volume":"6","author":"Miller","year":"2017","journal-title":"Elife"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Labadorf, A.T., and Myers, R.H. (2015). Evidence of extensive alternative splicing in post mortem human brain HTT transcription by mRNA sequencing. PLOS ONE, 10.","DOI":"10.1371\/journal.pone.0141298"},{"key":"ref_49","first-page":"1825","article-title":"Correlation of high-resolution magic angle spinning proton magnetic resonance spectroscopy with histopathology of intact human brain tumor specimens","volume":"58","author":"Cheng","year":"1998","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/nbm.1296","article-title":"An assessment of the effects of sample ischaemia and spinning time on the metabolic profile of brain tumour biopsy specimens as determined by high-resolution magic angle spinning [1H]NMR","volume":"21","author":"Opstad","year":"2008","journal-title":"NMR Biomed."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6181","DOI":"10.1073\/pnas.1019164108","article-title":"Rapid metabolic evolution in human prefrontal cortex","volume":"108","author":"Fu","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1016\/j.chembiol.2014.09.016","article-title":"Brain region mapping using global metabolomics","volume":"21","author":"Ivanisevic","year":"2014","journal-title":"Chem. Biol."},{"key":"ref_53","first-page":"60","article-title":"NextGen Brain Microdialysis: Applying modern metabolomics technology to the analysis of extracellular fluid in the central nervous system","volume":"1","author":"Kao","year":"2015","journal-title":"Mol. Neuropsychiatry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1001\/jamaneurol.2017.1200","article-title":"Association between motor symptoms and brain metabolism in early Huntington disease","volume":"74","author":"Gaura","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3233\/JHD-150170","article-title":"Brain cholesterol synthesis and metabolism is progressively disturbed in the R6\/1 mouse model of Huntington\u2019s disease: A targeted GC-MS\/MS sterol analysis","volume":"4","author":"Kreilaus","year":"2015","journal-title":"J. Huntington\u2019s Dis."},{"key":"ref_56","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":"ref_57","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 form Huntington\u2019s disease patients","volume":"11","author":"Naseri","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1212\/01.WNL.0000094120.09977.92","article-title":"Compound heterozygous PANK2 mutations confirm HARP and Hallervorden-Spatz syndromes are allelic","volume":"61","author":"Houlden","year":"2003","journal-title":"Neurology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1750-1172-6-68","article-title":"Neuroacanthocytosis syndromes","volume":"6","author":"Jung","year":"2011","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1001\/archneur.56.5.569","article-title":"Increased basal ganglia iron levels in Huntington disease","volume":"56","author":"Bartzokis","year":"1999","journal-title":"Arch. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.bbadis.2011.06.016","article-title":"Neurodegeneration with brain iron accumulation\u2014Clinical symptoms and neuroimaging","volume":"1822","author":"Schipper","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Shurubor, Y.I., D\u2019Aurelio, M., Clark-Matott, J., Isakova, E.P., Deryabina, Y.I., Beal, M.F., Cooper, A.J.L., and Krasnikov, B.F. (2017). Determination of coenzyme A and acetyl-coenzyme A in biological samples using HPLC with UV detection. Molecules, 22.","DOI":"10.3390\/molecules22091388"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1152\/physrev.1990.70.3.701","article-title":"Nitrogen metabolism and ornithine cycle function","volume":"70","author":"Meijer","year":"1990","journal-title":"Physiol. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0307-4412(99)00041-2","article-title":"Connecting links between the urea cycle and the TCA cycle: A Tutorial exercise","volume":"27","author":"Anand","year":"1999","journal-title":"Biochem. Educ."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1146\/annurev.ne.09.030186.002041","article-title":"Parallel organization of functionally segregated circuits linking basal ganglia and cortex","volume":"9","author":"Alexander","year":"1986","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/978-3-319-57193-5_5","article-title":"The complexity of clinical Huntington\u2019s disease: Developments in molecular genetics, neuropathology and neuroimaging biomarkers","volume":"15","author":"Tippett","year":"2017","journal-title":"Adv. Neurobiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S1474-4422(11)70263-0","article-title":"Potential endpoints for clinical trials in premanifest and early Huntington\u2019s disease in the TRACK-HD study: Analysis of 24 month observational data","volume":"11","author":"Tabrizi","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1159\/000443556","article-title":"Fatty acid beta-oxidation disorders: A Brief review","volume":"23","author":"Vishwanath","year":"2016","journal-title":"Ann. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1172\/JCI103756","article-title":"Pantothenic acid deficiency in man","volume":"37","author":"Hodges","year":"1958","journal-title":"J. Clin. Investig."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/bs.vh.2014.12.003","article-title":"The sodium\/multivitamin transporter (SMVT): A multipotent system with therapeutic implications","volume":"98","author":"Quick","year":"2015","journal-title":"Vitam. Horm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1111\/j.1471-4159.1986.tb00705.x","article-title":"Pantothenic acid transport through the blood-brain barrier","volume":"47","author":"Spector","year":"1986","journal-title":"J. Neurochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"G64","DOI":"10.1152\/ajpgi.00379.2012","article-title":"Conditional knockout of the Slc5a6 gene in mouse intestine impairs biotin absorption","volume":"304","author":"Ghosal","year":"2013","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s00439-016-1751-x","article-title":"Mutations in SLC5A6 associated with brain, immune, bone and intestinal dysfunction in a young child","volume":"136","author":"Subramanian","year":"2017","journal-title":"Hum. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1016\/S0021-9258(19)42811-1","article-title":"Choline acetyltransferase. Inhibition by thiol reagents","volume":"249","author":"Roskoski","year":"1973","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/j.1476-5381.1968.tb00472.x","article-title":"The effect of some drugs on the \u201cfree\u201d and \u201cbound\u201d acetylcholine content of rat brain","volume":"33","author":"Crossland","year":"1968","journal-title":"Br. J. Pharmacol. Chemother."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3547","DOI":"10.1073\/pnas.93.8.3547","article-title":"Visualization of the vesicular acetylcholine transporter in cholinergic nerve terminals and its targeting to a specific population of small synaptic vesicles","volume":"93","author":"Weihe","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.molcel.2014.01.016","article-title":"Regulation of autophagy by cytosolic acetyl-coenzyme A","volume":"53","author":"Pietrocola","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.celrep.2016.10.012","article-title":"Lipids reprogram metabolism to become a major carbon source for histone acetylation","volume":"17","author":"McDonnell","year":"2016","journal-title":"Cell Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1038\/nprot.2011.335","article-title":"Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry","volume":"6","author":"Dunn","year":"2011","journal-title":"Nat. Protoc."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Ioannidis, J.P.A. (2005). Why most published research findings are false. PLoS Med., 2.","DOI":"10.1371\/journal.pmed.0020124"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nrn3475","article-title":"Power failure: Why small sample size undermines the reliability of neuroscience","volume":"14","author":"Button","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_82","unstructured":"Di Meo, I., Carecchio, M., and Tiranti, V. (2018). Inborn errors of coenzyme A metabolism and neurodegeneration. J. Inherit. Metab., 1\u20137."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"7038","DOI":"10.1021\/ac9011599","article-title":"Development and performance of a gas chromatography\u2013time-of-flight mass spectrometry analysis for large-scale nontargeted metabolomic studies of human serum","volume":"81","author":"Begley","year":"2009","journal-title":"Anal. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.chroma.2013.01.097","article-title":"Alkylsilyl derivatives for gas chromatography","volume":"1296","author":"Poole","year":"2013","journal-title":"J. Chromatogr. A"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1039\/C7MT00074J","article-title":"Evidence for widespread, severe brain copper deficiency in Alzheimer\u2019s dementia","volume":"9","author":"Xu","year":"2017","journal-title":"Metallomics"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. Stat. Soc. Ser. B (Stat. Methodol.)"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/9\/6\/113\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:57:26Z","timestamp":1760187446000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/9\/6\/113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,11]]},"references-count":86,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["metabo9060113"],"URL":"https:\/\/doi.org\/10.3390\/metabo9060113","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,11]]}}}