{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:52:00Z","timestamp":1792036320902,"version":"4.4.0"},"reference-count":100,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Huntington\u2019s disease is a devastating neurodegenerative disorder that onsets in late adulthood as progressive and terminal cognitive, psychiatric and motor deficits. The disease is genetic, triggered by a CAG repeat (polyQ) expansion mutation in the Huntingtin gene and resultant huntingtin protein. Although the mutant huntingtin protein is ubiquitously expressed, the striatum degenerates early and consistently in the disease. The polyQ mutation at the N-terminus of the huntingtin protein alters its natural interactions with neural phospholipids in vitro, suggesting that the specific lipid composition of brain regions could influence their vulnerability to interference by mutant huntingtin; however, this has not yet been demonstrated in vivo. Sphingolipids are critical cell signalling molecules, second messengers and membrane components. Despite evidence of sphingolipid disturbance in Huntington\u2019s mouse and cell models, there is limited knowledge of how these lipids are affected in human brain tissue. Using post-mortem brain tissue from five brain regions implicated in Huntington\u2019s disease (control n\u2009=\u200913, Huntington\u2019s n\u2009=\u200913), this study aimed to identify where and how sphingolipid species are affected in the brain of clinically advanced Huntington\u2019s cases. Sphingolipids were extracted from the tissue and analysed using targeted mass spectrometry analysis; proteins were analysed by western blot. The caudate, putamen and cerebellum had distinct sphingolipid changes in Huntington\u2019s brain whilst the white and grey frontal cortex were spared. The caudate of Huntington\u2019s patients had a shifted sphingolipid profile, favouring long (C13\u2013C21) over very-long-chain (C22\u2013C26) ceramides, sphingomyelins and lactosylceramides. Ceramide synthase 1, which synthesizes the long-chain sphingolipids, had a reduced expression in Huntington\u2019s caudate, correlating positively with a younger age at death and a longer CAG repeat length of the Huntington\u2019s patients. The expression of ceramide synthase 2, which synthesizes very-long-chain sphingolipids, was not different in Huntington\u2019s brain. However, there was evidence of possible post-translational modifications in the Huntington\u2019s patients only. Post-translational modifications to ceramide synthase 2 may be driving the distinctive sphingolipid profile shifts of the caudate in advanced Huntington\u2019s disease. This shift in the sphingolipid profile is also found in the most severely affected brain regions of several other neurodegenerative conditions and may be an important feature of region-specific cell dysfunction in neurodegenerative disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcab303","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T12:56:04Z","timestamp":1640177764000},"source":"Crossref","is-referenced-by-count":34,"title":["The long and the short of Huntington\u2019s disease: how the sphingolipid profile is shifted in the caudate of advanced clinical cases"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9014-2771","authenticated-orcid":false,"given":"Gabrielle R.","family":"Phillips","sequence":"first","affiliation":[{"name":"Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia"},{"name":"School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia"},{"name":"Molecular Horizons, University of Wollongong, Wollongong, NSW 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer T.","family":"Saville","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Pathology, SA Pathology at Women\u2019s and Children\u2019s Hospital, North Adelaide, SA 5006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Hancock","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon H. J.","family":"Brown","sequence":"additional","affiliation":[{"name":"Molecular Horizons, University of Wollongong, Wollongong, NSW 2522, Australia"},{"name":"School of Chemistry and Molecular Biosciences, University of Wollongong, Wollongong, NSW 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Jenner","sequence":"additional","affiliation":[{"name":"Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catriona","family":"McLean","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Alfred Health and Florey Neuroscience, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Fuller","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Pathology, SA Pathology at Women\u2019s and Children\u2019s Hospital, North Adelaide, SA 5006, Australia"},{"name":"Adelaide Medical School, University of Adelaide, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A.","family":"Newell","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia"},{"name":"School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia"},{"name":"Molecular Horizons, University of Wollongong, Wollongong, NSW 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd W.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia"},{"name":"School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia"},{"name":"Molecular Horizons, University of Wollongong, Wollongong, NSW 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"2022021509234158300_fcab303-B1","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 disease chromosomes","volume":"72","author":"Macdonald","year":"1993","journal-title":"Cell"},{"key":"2022021509234158300_fcab303-B2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ajhg.2015.12.018","article-title":"The HTT CAG-expansion mutation determines age at death but not disease duration in Huntington disease","volume":"98","author":"Keum","year":"2016","journal-title":"Am J Hum Genet"},{"key":"2022021509234158300_fcab303-B3","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1001\/archneur.58.2.273","article-title":"Progression of symptoms in the early and middle stages of Huntington disease","volume":"58","author":"Kirkwood","year":"2001","journal-title":"Arch Neurol"},{"key":"2022021509234158300_fcab303-B4","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/nrn1806","article-title":"Normal huntingtin function: An alternative approach to Huntington\u2019s disease","volume":"6","author":"Cattaneo","year":"2005","journal-title":"Nat Rev Neurosci"},{"key":"2022021509234158300_fcab303-B5","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.celrep.2019.12.069","article-title":"Striatal projection neurons require huntingtin for synaptic connectivity and survival","volume":"30","author":"Burrus","year":"2020","journal-title":"Cell Rep"},{"key":"2022021509234158300_fcab303-B6","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.neuron.2016.02.003","article-title":"The biology of huntingtin","volume":"89","author":"Saudou","year":"2016","journal-title":"Neuron"},{"key":"2022021509234158300_fcab303-B7","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/ncb3101","article-title":"Huntingtin functions as a scaffold for selective macroautophagy","volume":"17","author":"Rui","year":"2015","journal-title":"Nat Cell Biol"},{"key":"2022021509234158300_fcab303-B8","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1212\/01.WNL.0000132965.14653.D1","article-title":"Onset and rate of striatal atrophy in preclinical Huntington disease","volume":"63","author":"Aylward","year":"2004","journal-title":"Neurology"},{"key":"2022021509234158300_fcab303-B9","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1006\/exnr.1998.6919","article-title":"Regional specificity of brain atrophy in huntington\u2019s disease","volume":"154","author":"Halliday","year":"1998","journal-title":"Exp Neurol"},{"key":"2022021509234158300_fcab303-B10","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/00005072-198809000-00003","article-title":"Morphometric demonstration of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington\u2019s disease","volume":"47","author":"de la Monte","year":"1988","journal-title":"J Neuropathol Exp Neurol"},{"key":"2022021509234158300_fcab303-B11","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3389\/fnins.2013.00233","article-title":"The role of the striatum in social behavior","volume":"7","author":"B\u00e1ez-Mendoza","year":"2013","journal-title":"Front Neurosci"},{"key":"2022021509234158300_fcab303-B12","first-page":"947","article-title":"Anatomy of the corpus striatum and brain stem integrating systems","volume-title":"Comprehensive physiology","author":"Carpenter","year":"2011"},{"key":"2022021509234158300_fcab303-B13","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.brainresbull.2006.10.028","article-title":"Change in MRI striatal volumes as a biomarker in preclinical Huntington\u2019s disease","volume":"72","author":"Aylward","year":"2007","journal-title":"Brain Res Bull"},{"key":"2022021509234158300_fcab303-B14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.0305-1846.2001.00299.x","article-title":"The selective vulnerability of nerve cells in Huntington\u2019s disease","volume":"27","author":"Sieradzan","year":"2001","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2022021509234158300_fcab303-B15","doi-asserted-by":"crossref","first-page":"183497","DOI":"10.1016\/j.bbamem.2020.183497","article-title":"Lipid headgroups alter huntingtin aggregation on membranes","volume":"1863","author":"Beasley","year":"2021","journal-title":"Biochim Biophys Acta \u2013 Biomembr"},{"key":"2022021509234158300_fcab303-B16","doi-asserted-by":"crossref","first-page":"36464","DOI":"10.1074\/jbc.M503672200","article-title":"Huntingtin associates with acidic phospholipids at the plasma membrane","volume":"280","author":"Kegel","year":"2005","journal-title":"J Biol Chem"},{"key":"2022021509234158300_fcab303-B17","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.bbalip.2017.02.001","article-title":"Region-specific vulnerability to lipid peroxidation and evidence of neuronal mechanisms for polyunsaturated fatty acid biosynthesis in the healthy adult human central nervous system","volume":"1862","author":"Naud\u00ed","year":"2017","journal-title":"Biochim Biophys Acta \u2013 Mol Cell Biol Lipids"},{"key":"2022021509234158300_fcab303-B18","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1002\/jcp.24315","article-title":"Analysis of the protein network of cholesterol homeostasis in different brain regions: An age and sex dependent perspective","volume":"228","author":"Segatto","year":"2013","journal-title":"J Cell Physiol"},{"key":"2022021509234158300_fcab303-B19","doi-asserted-by":"crossref","first-page":"698","DOI":"10.3389\/fnins.2017.00698","article-title":"De novo synthesis of sphingolipids is defective in experimental models of huntington\u2019s disease","volume":"11","author":"Di Pardo","year":"2017","journal-title":"Front Neurosci"},{"key":"2022021509234158300_fcab303-B20","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/nan.12286","article-title":"Evidence for altered cholesterol metabolism in Huntington\u2019s disease post mortem brain tissue: Altered cholesterol metabolism in Huntington\u2019s disease","volume":"42","author":"Kreilaus","year":"2016","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2022021509234158300_fcab303-B21","doi-asserted-by":"crossref","first-page":"20314","DOI":"10.1038\/s41598-020-76973-8","article-title":"Cholesteryl ester levels are elevated in the caudate and putamen of Huntington\u2019s disease patients","volume":"10","author":"Phillips","year":"2020","journal-title":"Sci Rep"},{"key":"2022021509234158300_fcab303-B22","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.nbd.2007.05.003","article-title":"Glycolipid and ganglioside metabolism imbalances in huntington\u2019s disease","volume":"27","author":"Desplats","year":"2007","journal-title":"Neurobiol Dis"},{"key":"2022021509234158300_fcab303-B23","doi-asserted-by":"crossref","first-page":"6338","DOI":"10.1111\/febs.12559","article-title":"Glycosphingolipids: Synthesis and functions","volume":"280","author":"D\u2019Angelo","year":"2013","journal-title":"FEBS J"},{"key":"2022021509234158300_fcab303-B24","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1016\/j.bbamem.2009.08.016","article-title":"Sphingolipid\/cholesterol regulation of neurotransmitter receptor conformation and function","volume":"1788","author":"Fantini","year":"2009","journal-title":"Biochim Biophys Acta \u2013 Biomembr"},{"key":"2022021509234158300_fcab303-B25","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.plipres.2010.03.003","article-title":"Sterols and sphingolipids: Dynamic duo or partners in crime?","volume":"49","author":"Gulati","year":"2010","journal-title":"Prog Lipid Res"},{"key":"2022021509234158300_fcab303-B26","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2022021509234158300_fcab303-B27","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00018-012-1038-x","article-title":"Ceramide function in the brain: When a slight tilt is enough","volume":"70","author":"Mencarelli","year":"2013","journal-title":"Cell Mol Life Sci"},{"key":"2022021509234158300_fcab303-B28","doi-asserted-by":"crossref","first-page":"5677","DOI":"10.1074\/jbc.M707386200","article-title":"Characterization of ceramide synthase 2 tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate","volume":"283","author":"Laviad","year":"2008","journal-title":"J Biol Chem"},{"key":"2022021509234158300_fcab303-B29","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1042\/BJ20111626","article-title":"Ceramide synthases at the centre of sphingolipid metabolism and biology","volume":"441","author":"Mullen","year":"2012","journal-title":"Biochem J"},{"key":"2022021509234158300_fcab303-B30","article-title":"Properties of brain lipids","volume-title":"Basic neurochemistry: Molecular, cellular and medical aspects","author":"Agranoff","year":"1999"},{"key":"2022021509234158300_fcab303-B31","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.plipres.2011.11.001","article-title":"Chain length-specific properties of ceramides","volume":"51","author":"Gr\u00f6sch","year":"2012","journal-title":"Prog Lipid Res"},{"key":"2022021509234158300_fcab303-B32","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s12017-010-8114-x","article-title":"The role of the ceramide acyl chain length in neurodegeneration: Involvement of ceramide synthases","volume":"12","author":"Ben-David","year":"2010","journal-title":"NeuroMol Med"},{"key":"2022021509234158300_fcab303-B33","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/iub.319","article-title":"Mammalian ceramide synthases","volume":"62","author":"Levy","year":"2010","journal-title":"IUBMB Life"},{"key":"2022021509234158300_fcab303-B34","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.bbalip.2014.12.016","article-title":"Metabolism and functions of lipids in myelin","volume":"1851","author":"Schmitt","year":"2015","journal-title":"Biochim Biophys Acta \u2013 Mol Cell Biol Lipids"},{"key":"2022021509234158300_fcab303-B35","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s00418-007-0344-0","article-title":"Differential expression of (dihydro)ceramide synthases in mouse brain: Oligodendrocyte-specific expression of CerS2\/Lass2","volume":"129","author":"Becker","year":"2008","journal-title":"Histochem Cell Biol"},{"key":"2022021509234158300_fcab303-B36","doi-asserted-by":"crossref","first-page":"5928","DOI":"10.1073\/pnas.1522071113","article-title":"Ectopic expression of ceramide synthase 2 in neurons suppresses neurodegeneration induced by ceramide synthase 1 deficiency","volume":"113","author":"Spassieva","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022021509234158300_fcab303-B37","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/mds.25729","article-title":"Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson\u2019s disease: Altered ceramide in Parkinson\u2019s disease","volume":"29","author":"Abbott","year":"2014","journal-title":"Mov Disord"},{"key":"2022021509234158300_fcab303-B38","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/1531-8249(200101)49:1<29::AID-ANA7>3.0.CO;2-B","article-title":"Quantitative neuropathological changes in presymptomatic Huntington\u2019s disease","volume":"49","author":"G\u00f3mez-Tortosa","year":"2001","journal-title":"Ann Neurol"},{"key":"2022021509234158300_fcab303-B39","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1097\/00005072-199111000-00005","article-title":"Decreased neuronal and increased oligodendroglial densities in Huntington\u2019s disease caudate nucleus","volume":"50","author":"Myers","year":"1991","journal-title":"J Neuropathol Exp Neurol"},{"key":"2022021509234158300_fcab303-B40","doi-asserted-by":"crossref","first-page":"13280","DOI":"10.1073\/pnas.93.23.13280","article-title":"Functional breakdown of the lipid bilayer of the myelin membrane in central and peripheral nervous system by disrupted galactocerebroside synthesis","volume":"93","author":"Bosio","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022021509234158300_fcab303-B41","doi-asserted-by":"crossref","first-page":"4072","DOI":"10.1523\/JNEUROSCI.6348-09.2010","article-title":"Impaired ganglioside metabolism in huntington\u2019s disease and neuroprotective role of GM1","volume":"30","author":"Maglione","year":"2010","journal-title":"J Neurosci"},{"key":"2022021509234158300_fcab303-B42","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/BF00495383","article-title":"A histochemical study in Huntington\u2019s disease and control cases","volume":"58","author":"den Hartog Jager","year":"1978","journal-title":"Histochemistry"},{"key":"2022021509234158300_fcab303-B43","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1111\/jnc.14468","article-title":"Subventricular zone lipidomic architecture loss in Huntington\u2019s disease","volume":"146","author":"Hunter","year":"2018","journal-title":"J Neurochem"},{"key":"2022021509234158300_fcab303-B44","doi-asserted-by":"crossref","first-page":"20314","DOI":"10.1038\/s41598-020-76973-8","article-title":"Cholesteryl ester levels are elevated in the caudate and putamen of Huntington\u2019s disease patients","volume":"10","author":"Phillips","year":"2020","journal-title":"Sci Rep"},{"key":"2022021509234158300_fcab303-B45","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0022-510X(81)90108-8","article-title":"Accumulation of very long chain fatty acids is common to 3 variants of adrenoleukodystrophy (ALD)","volume":"51","author":"Molzer","year":"1981","journal-title":"J Neurol Sci"},{"key":"2022021509234158300_fcab303-B46","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0022-510X(92)90028-J","article-title":"Phospholipids in X-linked adrenoleukodystrophy white matter: Fatty acid abnormalities before the onset of demyelination","volume":"110","author":"Theda","year":"1992","journal-title":"J Neurol Sci"},{"key":"2022021509234158300_fcab303-B47","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1097\/00005072-198511000-00003","article-title":"Neuropathological classification of Huntington\u2019s disease","volume":"44","author":"Vonsattel","year":"1985","journal-title":"J Neuropathol Exp Neurol"},{"key":"2022021509234158300_fcab303-B48","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1194\/jlr.S120001025","article-title":"Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures","volume":"61","author":"Liebisch","year":"2020","journal-title":"J Lipid Res"},{"key":"2022021509234158300_fcab303-B49","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1194\/jlr.D700041-JLR200","article-title":"Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics","volume":"49","author":"Matyash","year":"2008","journal-title":"J Lipid Res"},{"key":"2022021509234158300_fcab303-B50","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s11745-013-3760-z","article-title":"An improved high-throughput lipid extraction method for the analysis of human brain lipids","volume":"48","author":"Abbott","year":"2013","journal-title":"Lipids"},{"key":"2022021509234158300_fcab303-B51","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1016\/j.bbalip.2016.08.016","article-title":"Regulation of glucose homeostasis and insulin action by ceramide acyl-chain length: A beneficial role for very long-chain sphingolipid species","volume":"1861","author":"Montgomery","year":"2016","journal-title":"Biochim Biophys Acta \u2013 Mol Cell Biol Lipids"},{"key":"2022021509234158300_fcab303-B52","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1194\/jlr.M800601-JLR200","article-title":"Caveolin-1-dependent and -independent membrane domains","volume":"50","author":"Le Lay","year":"2009","journal-title":"J Lipid Res"},{"key":"2022021509234158300_fcab303-B53","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ymgme.2019.08.008","article-title":"Sphingolipid dyshomeostasis in the brain of the mouse model of mucopolysaccharidosis type IIIA","volume":"129","author":"Saville","year":"2020","journal-title":"Mol Genet Metab"},{"key":"2022021509234158300_fcab303-B54","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/jnc.13976","article-title":"Subregional brain distribution of simple and complex glycosphingolipids in the mucopolysaccharidosis type I (Hurler syndrome) mouse: Impact of diet","volume":"141","author":"Saville","year":"2017","journal-title":"J Neurochem"},{"key":"2022021509234158300_fcab303-B55","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J Biol Chem"},{"key":"2022021509234158300_fcab303-B56","doi-asserted-by":"crossref","first-page":"4773","DOI":"10.1038\/ncomms5773","article-title":"A female gametocyte-specific ABC transporter plays a role in lipid metabolism in the malaria parasite","volume":"5:","author":"Tran","year":"2014","journal-title":"Nat Commun"},{"key":"2022021509234158300_fcab303-B57","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.bbalip.2008.04.002","article-title":"Human lens lipids differ markedly from those of commonly used experimental animals","volume":"1781","author":"Deeley","year":"2008","journal-title":"Biochim Biophys Acta \u2013 Mol Cell Biol Lipids"},{"key":"2022021509234158300_fcab303-B58","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1111\/j.1471-4159.2010.06964.x","article-title":"Cerebellar lipid differences between R6\/1 transgenic mice and humans with Huntington\u2019s disease: Cerebellar lipids in Huntington\u2019s disease","volume":"115","author":"Denny","year":"2010","journal-title":"J Neurochem"},{"key":"2022021509234158300_fcab303-B59","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1016\/j.bbadis.2018.04.012","article-title":"Targeted biochemical profiling of brain from Huntington\u2019s disease patients reveals novel metabolic pathways of interest","volume":"1864","author":"Graham","year":"2018","journal-title":"Biochim Biophys Acta \u2013 Mol Basis Dis"},{"key":"2022021509234158300_fcab303-B60","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1016\/j.bbamem.2013.04.025","article-title":"Huntingtin disrupts lipid bilayers in a polyQ-length dependent manner","volume":"1828","author":"Burke","year":"2013","journal-title":"Biochim Biophys Acta \u2013 Biomembr"},{"key":"2022021509234158300_fcab303-B61","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1111\/j.1471-4159.2009.06255.x","article-title":"Polyglutamine expansion in huntingtin alters its interaction with phospholipids","volume":"110","author":"Kegel","year":"2009","journal-title":"J Neurochem"},{"key":"2022021509234158300_fcab303-B62","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1016\/j.biocel.2013.06.004","article-title":"Ceramide metabolism in mouse tissue","volume":"45","author":"Schiffmann","year":"2013","journal-title":"Int J Biochem Cell Biol"},{"key":"2022021509234158300_fcab303-B63","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1177\/2472555217719372","article-title":"Tissue localization of glycosphingolipid accumulation in a gaucher disease mouse brain by LC-ESI-MS\/MS and high-resolution MALDI imaging mass spectrometry","volume":"22","author":"Jones","year":"2017","journal-title":"SLAS Discov Adv Sci Drug Discov"},{"key":"2022021509234158300_fcab303-B64","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/S0022-2275(20)39652-8","article-title":"Fatty acid composition of human brain sphingomyelins: Normal variation with age and changes during myelin disorders","volume":"6","author":"St\u00e4llberg-Stenhagen","year":"1965","journal-title":"J Lipid Res"},{"key":"2022021509234158300_fcab303-B65","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0022-510X(92)90028-J","article-title":"Phospholipids in X-linked adrenoleukodystrophy white matter: Fatty acid abnormalities before the onset of demyelination","volume":"110","author":"Theda","year":"1992","journal-title":"J Neurol Sci"},{"key":"2022021509234158300_fcab303-B66","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1093\/oxfordjournals.jbchem.a134942","article-title":"Fatty acid elongation activity in fibroblasts from patients with adrenoleukodystrophy (ALD)","volume":"96","author":"Tsuji","year":"1984","journal-title":"J Biochem"},{"key":"2022021509234158300_fcab303-B67","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12974-019-1436-1","article-title":"Astrocytic ceramide as possible indicator of neuroinflammation","volume":"16","author":"de Wit","year":"2019","journal-title":"J Neuroinflammation"},{"key":"2022021509234158300_fcab303-B68","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0006-8993(71)90478-1","article-title":"Lipid alterations in apparently normal white matter in multiple sclerosis","volume":"35","author":"Alling","year":"1971","journal-title":"Brain Res"},{"key":"2022021509234158300_fcab303-B69","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/1044-5765(92)90015-T","article-title":"Dopamine and basal ganglia disorders in humans","volume":"4","author":"Marsden","year":"1992","journal-title":"Semin Neurosci"},{"key":"2022021509234158300_fcab303-B70","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/brain\/awg119","article-title":"Progressive striatal and cortical dopamine receptor dysfunction in Huntington\u2019s disease: A PET study","volume":"126","author":"Pavese","year":"2003","journal-title":"Brain"},{"key":"2022021509234158300_fcab303-B71","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fncir.2013.00019","article-title":"Role of cerebral cortex in the neuropathology of Huntington\u2019s disease","volume":"7","author":"Estrada-S\u00e1nchez","year":"2013","journal-title":"Front Neural Circuits"},{"key":"2022021509234158300_fcab303-B72","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1002\/jnr.23763","article-title":"How membrane dysfunction influences neuronal survival pathways in sphingolipid storage disorders","volume":"94","author":"Sural-Fehr","year":"2016","journal-title":"J Neurosci Res"},{"key":"2022021509234158300_fcab303-B73","doi-asserted-by":"crossref","first-page":"7485","DOI":"10.1073\/pnas.1804266115","article-title":"Traceless synthesis of ceramides in living cells reveals saturation-dependent apoptotic effects","volume":"115","author":"Rudd","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022021509234158300_fcab303-B74","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.bbamem.2014.11.018","article-title":"Very long chain ceramides interfere with C16-ceramide-induced channel formation: A plausible mechanism for regulating the initiation of intrinsic apoptosis","volume":"1848","author":"Stiban","year":"2015","journal-title":"Biochim Biophys Acta \u2013 Biomembr"},{"key":"2022021509234158300_fcab303-B75","doi-asserted-by":"crossref","first-page":"7477","DOI":"10.1074\/jbc.M115.695858","article-title":"Enzyme activities of the ceramide synthases CERS2\u20136 are regulated by phosphorylation in the C-terminal region","volume":"291","author":"Sassa","year":"2016","journal-title":"J Biol Chem"},{"key":"2022021509234158300_fcab303-B76","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1042\/BJ20050291","article-title":"Mammalian Lass6 and its related family members regulate synthesis of specific ceramides","volume":"390","author":"Mizutani","year":"2005","journal-title":"Biochem J"},{"key":"2022021509234158300_fcab303-B77","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.bbalip.2012.04.008","article-title":"A shift in sphingolipid composition from C24 to C16 increases susceptibility to apoptosis in HeLa cells","volume":"1821","author":"Sassa","year":"2012","journal-title":"Biochim Biophys Acta \u2013 Mol Cell Biol Lipids"},{"key":"2022021509234158300_fcab303-B78","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/978-3-319-71779-1_3","article-title":"Mitochondrial dysfunction in Huntington\u2019s disease","volume":"1049","author":"Carmo","year":"2018","journal-title":"Adv Exp Med Biol"},{"key":"2022021509234158300_fcab303-B79","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1194\/jlr.M026062","article-title":"Raft-like microdomains play a key role in mitochondrial impairment in lymphoid cells from patients with Huntington\u2019s disease","volume":"53","author":"Ciarlo","year":"2012","journal-title":"J Lipid Res"},{"key":"2022021509234158300_fcab303-B80","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.bbadis.2009.07.012","article-title":"Mitochondria in Huntington\u2019s disease","volume":"1802","author":"Damiano","year":"2010","journal-title":"Biochim Biophys Acta \u2013 Mol Basis Dis"},{"key":"2022021509234158300_fcab303-B81","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.nbd.2015.09.008","article-title":"Mitochondrial dynamics and quality control in Huntington\u2019s disease","volume":"90","author":"Guedes-Dias","year":"2016","journal-title":"Neurobiol Dis"},{"key":"2022021509234158300_fcab303-B82","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.1093\/hmg\/ddq306","article-title":"Mitochondrial loss, dysfunction and altered dynamics in Huntington\u2019s disease","volume":"19","author":"Kim","year":"2010","journal-title":"Hum Mol Genet"},{"key":"2022021509234158300_fcab303-B83","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1001\/jamaneurol.2019.2368","article-title":"Association of CAG repeats with long-term progression in Huntington disease","volume":"76","author":"Langbehn","year":"2019","journal-title":"JAMA Neurol"},{"key":"2022021509234158300_fcab303-B84","doi-asserted-by":"crossref","first-page":"795","DOI":"10.3233\/JAD-160551","article-title":"Altered sphingolipid balance in capillary cerebral amyloid angiopathy","volume":"60","author":"de Wit","year":"2017","journal-title":"J Alzheimer\u2019s Dis"},{"key":"2022021509234158300_fcab303-B85","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1111\/j.1471-4159.2008.05490.x","article-title":"Differential regulation of sphingomyelin synthesis and catabolism in oligodendrocytes and neurons","volume":"106","author":"Kilkus","year":"2008","journal-title":"J Neurochem"},{"key":"2022021509234158300_fcab303-B86","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/0014-5793(95)00695-6","article-title":"Sphingomyelin is synthesised at the plasma membrane of oligodendrocytes and by purified myelin membranes: A study with fluorescent- and radio-labelled ceramide analogues","volume":"368","author":"Vos","year":"1995","journal-title":"FEBS Lett"},{"key":"2022021509234158300_fcab303-B87","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1111\/j.1471-4159.2007.04822.x","article-title":"Lactosylceramide: A lipid second messenger in neuroinflammatory disease","volume":"103","author":"Won","year":"2007","journal-title":"J Neurochem"},{"key":"2022021509234158300_fcab303-B88","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s10495-015-1098-0","article-title":"Lactosylceramide-accumulation in lipid-rafts mediate aberrant-autophagy, inflammation and apoptosis in cigarette smoke induced emphysema","volume":"20","author":"Bodas","year":"2015","journal-title":"Apoptosis"},{"key":"2022021509234158300_fcab303-B89","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.3390\/biom10071083","article-title":"Sphingolipid analysis indicate lactosylceramide as a potential biomarker of inflammatory bowel disease in children","volume":"10","author":"Filimoniuk","year":"2020","journal-title":"Biomolecules"},{"key":"2022021509234158300_fcab303-B90","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1750-3639.2012.00629.x","article-title":"Degeneration of the cerebellum in Huntington\u2019s disease (HD): Possible relevance for the clinical picture and potential gateway to pathological mechanisms of the disease process","volume":"23","author":"R\u00fcb","year":"2013","journal-title":"Brain Pathol"},{"key":"2022021509234158300_fcab303-B91","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/cercor\/bhu250","article-title":"Functional segregation of the human dorsomedial prefrontal cortex","volume":"26","author":"Eickhoff","year":"2016","journal-title":"Cereb Cortex"},{"key":"2022021509234158300_fcab303-B92","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.1002\/hbm.22835","article-title":"Prefrontal cortex white matter tracts in prodromal Huntington disease: Prefrontal cortex WM tracts in prodromal HD","volume":"36","author":"Matsui","year":"2015","journal-title":"Hum Brain Mapp"},{"key":"2022021509234158300_fcab303-B93","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11357-017-9961-2","article-title":"The phospholipid composition of the human entorhinal cortex remains relatively stable over 80 years of adult aging","volume":"39","author":"Hancock","year":"2017","journal-title":"GeroScience"},{"key":"2022021509234158300_fcab303-B94","first-page":"703","article-title":"Lipid profile in human frontal cortex is sustained throughout healthy adult life span to decay at advanced ages","volume":"73","author":"Cabr\u00e9","year":"2018","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2022021509234158300_fcab303-B95","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1212\/01.WNL.0000138434.68093.67","article-title":"In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease","volume":"63","author":"Fennema-Notestine","year":"2004","journal-title":"Neurology"},{"key":"2022021509234158300_fcab303-B96","first-page":"213","article-title":"Topography of cerebral atrophy in early Huntington\u2019s disease: A voxel based morphometric MRI study","volume":"75","author":"Kassubek","year":"2004","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2022021509234158300_fcab303-B97","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.nicl.2016.02.014","article-title":"Linking white matter and deep gray matter alterations in premanifest Huntington disease","volume":"11","author":"Faria","year":"2016","journal-title":"NeuroImage Clin"},{"key":"2022021509234158300_fcab303-B98","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1093\/brain\/awn025","article-title":"Cerebral cortex and the clinical expression of Huntington\u2019s disease: Complexity and heterogeneity","volume":"131","author":"Rosas","year":"2008","journal-title":"Brain"},{"key":"2022021509234158300_fcab303-B99","doi-asserted-by":"crossref","first-page":"5280","DOI":"10.1038\/s41598-017-05709-y","article-title":"Defective sphingosine-1-phosphate metabolism is a druggable target in Huntington\u2019s disease","volume":"7","author":"Di Pardo","year":"2017","journal-title":"Sci Rep"},{"key":"2022021509234158300_fcab303-B100","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jnutbio.2015.12.001","article-title":"Metabolic disturbances in plasma as biomarkers for Huntington\u2019s disease","volume":"31","author":"Cheng","year":"2016","journal-title":"J Nutr Biochem"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcab303\/41904706\/fcab303.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/4\/1\/fcab303\/42470274\/fcab303.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/4\/1\/fcab303\/42470274\/fcab303.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T19:25:57Z","timestamp":1699989957000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcab303\/6481514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,23]]},"references-count":100,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1,4]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcab303","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,2,1]]},"published":{"date-parts":[[2021,12,23]]},"article-number":"fcab303"}}