{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:52:29Z","timestamp":1792036349877,"version":"4.4.0"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T00:00:00Z","timestamp":1560470400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T00:00:00Z","timestamp":1560470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"published-print":{"date-parts":[[2019,11]]},"DOI":"10.1007\/s00401-019-02019-7","type":"journal-article","created":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T22:02:31Z","timestamp":1560463351000},"page":"837-858","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Restoring brain cholesterol turnover improves autophagy and has therapeutic potential in mouse models of spinocerebellar ataxia"],"prefix":"10.1007","volume":"138","author":[{"given":"Cl\u00e9vio","family":"N\u00f3brega","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Mendon\u00e7a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Marcelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonin","family":"Lamazi\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Tom\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetan","family":"Despres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Matos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatich","family":"Mechmet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Langui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred","family":"den Dunnen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Pereira","family":"de Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Cartier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1396-7523","authenticated-orcid":false,"given":"Sandro","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,14]]},"reference":[{"key":"2019_CR1","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1007\/s00401-014-1289-8","volume":"128","author":"S Alves","year":"2014","unstructured":"Alves S, Cormier-Dequaire F, Marinello M, Marais T, Muriel MP, Beaumatin F et al (2014) The autophagy\/lysosome pathway is impaired in SCA7 patients and SCA7 knock-in mice. Acta Neuropathol 128:705\u2013722. https:\/\/doi.org\/10.1007\/s00401-014-1289-8","journal-title":"Acta Neuropathol"},{"key":"2019_CR2","doi-asserted-by":"publisher","first-page":"e3341","DOI":"10.1371\/journal.pone.0003341","volume":"3","author":"S Alves","year":"2008","unstructured":"Alves S, Nascimento-Ferreira I, Auregan G, Hassig R, Dufour N, Brouillet E et al (2008) Allele-specific RNA silencing of mutant ataxin-3 mediates neuroprotection in a rat model of Machado\u2013Joseph disease. PLoS One 3:e3341. https:\/\/doi.org\/10.1371\/journal.pone.0003341","journal-title":"PLoS One"},{"key":"2019_CR3","doi-asserted-by":"publisher","first-page":"2380","DOI":"10.1093\/hmg\/ddq111","volume":"19","author":"S Alves","year":"2010","unstructured":"Alves S, Nascimento-Ferreira I, Dufour N, Hassig R, Auregan G, Nobrega C et al (2010) Silencing ataxin-3 mitigates degeneration in a rat model of Machado\u2013Joseph disease: no role for wild-type ataxin-3? Hum Mol Genet 19:2380\u20132394. https:\/\/doi.org\/10.1093\/hmg\/ddq111","journal-title":"Hum Mol Genet"},{"key":"2019_CR4","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1093\/hmg\/ddn106","volume":"17","author":"S Alves","year":"2008","unstructured":"Alves S, Regulier E, Nascimento-Ferreira I, Hassig R, Dufour N, Koeppen A et al (2008) Striatal and nigral pathology in a lentiviral rat model of Machado\u2013Joseph disease. Hum Mol Genet 17:2071\u20132083. https:\/\/doi.org\/10.1093\/hmg\/ddn106","journal-title":"Hum Mol Genet"},{"key":"2019_CR5","doi-asserted-by":"publisher","first-page":"E1642","DOI":"10.1073\/pnas.1416609112","volume":"112","author":"CA Aveleira","year":"2015","unstructured":"Aveleira CA, Botelho M, Carmo-Silva S, Pascoal JF (2015) Neuropeptide Y stimulates autophagy in hypothalamic neurons. Proc Natl Acad Sci 112:E1642\u2013E1651. https:\/\/doi.org\/10.1073\/pnas.1416609112","journal-title":"Proc Natl Acad Sci"},{"key":"2019_CR6","doi-asserted-by":"publisher","first-page":"211","DOI":"10.3389\/fnmol.2017.00211","volume":"10","author":"S Ayciriex","year":"2017","unstructured":"Ayciriex S, Djelti F, Alves S, Regazzetti A, Gaudin M, Varin J et al (2017) Neuronal cholesterol accumulation induced by Cyp46a1 down-regulation in mouse hippocampus disrupts brain lipid homeostasis. Front Mol Neurosci 10:211. https:\/\/doi.org\/10.3389\/fnmol.2017.00211","journal-title":"Front Mol Neurosci"},{"key":"2019_CR7","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/mt.2014.180","volume":"23","author":"JI Ayers","year":"2015","unstructured":"Ayers JI, Fromholt S, Sinyavskaya O, Siemienski Z, Rosario AM, Li A et al (2015) Widespread and efficient transduction of spinal cord and brain following neonatal AAV injection and potential disease modifying effect in ALS mice. Mol Ther 23:53\u201362. https:\/\/doi.org\/10.1038\/mt.2014.180","journal-title":"Mol Ther"},{"key":"2019_CR8","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1111\/j.1365-2796.2006.01725.x","volume":"260","author":"I Bjorkhem","year":"2006","unstructured":"Bjorkhem I (2006) Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med 260:493\u2013508. https:\/\/doi.org\/10.1111\/j.1365-2796.2006.01725.x","journal-title":"J Intern Med"},{"key":"2019_CR9","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1194\/jlr.R006338","volume":"51","author":"I Bjorkhem","year":"2010","unstructured":"Bjorkhem I, Leoni V, Meaney S (2010) Genetic connections between neurological disorders and cholesterol metabolism. J Lipid Res 51:2489\u20132503. https:\/\/doi.org\/10.1194\/jlr.R006338","journal-title":"J Lipid Res"},{"key":"2019_CR10","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1016\/S0022-2275(20)32188-X","volume":"39","author":"I Bjorkhem","year":"1998","unstructured":"Bjorkhem I, Lutjohann D, Diczfalusy U, Stahle L, Ahlborg G, Wahren J (1998) Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res 39:1594\u20131600","journal-title":"J Lipid Res"},{"key":"2019_CR11","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1161\/01.ATV.0000120374.59826.1b","volume":"24","author":"I Bjorkhem","year":"2004","unstructured":"Bjorkhem I, Meaney S (2004) Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol 24:806\u2013815. https:\/\/doi.org\/10.1161\/01.ATV.0000120374.59826.1b","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2019_CR12","doi-asserted-by":"publisher","first-page":"4638","DOI":"10.1038\/ncomms5638","volume":"5","author":"JR Blount","year":"2014","unstructured":"Blount JR, Tsou WL, Ristic G, Burr AA, Ouyang M, Galante H et al (2014) Ubiquitin-binding site 2 of ataxin-3 prevents its proteasomal degradation by interacting with Rad23. Nat Commun 5:4638. https:\/\/doi.org\/10.1038\/ncomms5638","journal-title":"Nat Commun"},{"key":"2019_CR13","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1093\/brain\/awv384","volume":"139","author":"L Boussicault","year":"2016","unstructured":"Boussicault L, Alves S, Lamaziere A, Planques A, Heck N, Moumne L et al (2016) CYP46A1, the rate-limiting enzyme for cholesterol degradation, is neuroprotective in Huntington\u2019s disease. Brain 139:953\u2013970. https:\/\/doi.org\/10.1093\/brain\/awv384","journal-title":"Brain"},{"key":"2019_CR14","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.nbd.2017.02.007","volume":"102","author":"J Branchu","year":"2017","unstructured":"Branchu J, Boutry M, Sourd L, Depp M, Leone C, Corriger A et al (2017) Loss of spatacsin function alters lysosomal lipid clearance leading to upper and lower motor neuron degeneration. Neurobiol Dis 102:21\u201337. https:\/\/doi.org\/10.1016\/j.nbd.2017.02.007","journal-title":"Neurobiol Dis"},{"key":"2019_CR15","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1007\/s004150050456","volume":"246","author":"K Burk","year":"1999","unstructured":"Burk K, Fetter M, Abele M, Laccone F, Brice A, Dichgans J et al (1999) Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3. J Neurol 246:789\u2013797","journal-title":"J Neurol"},{"key":"2019_CR16","doi-asserted-by":"publisher","first-page":"5965","DOI":"10.1093\/hmg\/ddv268","volume":"24","author":"MA Burlot","year":"2015","unstructured":"Burlot MA, Braudeau J, Michaelsen-Preusse K, Potier B, Ayciriex S, Varin J et al (2015) Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology. Hum Mol Genet 24:5965\u20135976. https:\/\/doi.org\/10.1093\/hmg\/ddv268","journal-title":"Hum Mol Genet"},{"key":"2019_CR17","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1111\/j.1742-4658.2008.06808.x","volume":"276","author":"N Camargo","year":"2009","unstructured":"Camargo N, Smit AB, Verheijen MH (2009) SREBPs: SREBP function in glia-neuron interactions. FEBS J 276:628\u2013636. https:\/\/doi.org\/10.1111\/j.1742-4658.2008.06808.x","journal-title":"FEBS J"},{"key":"2019_CR18","doi-asserted-by":"publisher","first-page":"9310","DOI":"10.1073\/pnas.152101299","volume":"99","author":"Y Chai","year":"2002","unstructured":"Chai Y, Shao J, Miller VM, Williams A, Paulson HL (2002) Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis. Proc Natl Acad Sci USA 99:9310\u20139315. https:\/\/doi.org\/10.1073\/pnas.152101299","journal-title":"Proc Natl Acad Sci USA"},{"key":"2019_CR19","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1002\/pd.1254","volume":"25","author":"F Chevy","year":"2005","unstructured":"Chevy F, Humbert L, Wolf C (2005) Sterol profiling of amniotic fluid: a routine method for the detection of distal cholesterol synthesis deficit. Prenat Diagn 25:1000\u20131006. https:\/\/doi.org\/10.1002\/pd.1254","journal-title":"Prenat Diagn"},{"key":"2019_CR20","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.mcn.2015.03.010","volume":"66","author":"CJ Cortes","year":"2015","unstructured":"Cortes CJ, La Spada AR (2015) Autophagy in polyglutamine disease: imposing order on disorder or contributing to the chaos? Mol Cell Neurosci 66:53\u201361. https:\/\/doi.org\/10.1016\/j.mcn.2015.03.010","journal-title":"Mol Cell Neurosci"},{"key":"2019_CR21","doi-asserted-by":"publisher","first-page":"11445","DOI":"10.1038\/ncomms11445","volume":"7","author":"J Cunha-Santos","year":"2016","unstructured":"Cunha-Santos J, Duarte-Neves J, Carmona V, Guarente L, Pereira de Almeida L, Cavadas C (2016) Caloric restriction blocks neuropathology and motor deficits in Machado\u2013Joseph disease mouse models through SIRT1 pathway. Nat Commun 7:11445. https:\/\/doi.org\/10.1038\/ncomms11445","journal-title":"Nat Commun"},{"key":"2019_CR22","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/nbt.3440","volume":"34","author":"BE Deverman","year":"2016","unstructured":"Deverman BE, Pravdo PL, Simpson BP, Kumar SR, Chan KY, Banerjee A et al (2016) Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain 34:204\u2013209. https:\/\/doi.org\/10.1038\/nbt.3440","journal-title":"Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain"},{"key":"2019_CR23","doi-asserted-by":"publisher","first-page":"3801","DOI":"10.1074\/jbc.R100057200","volume":"277","author":"JM Dietschy","year":"2002","unstructured":"Dietschy JM, Turley SD (2002) Control of cholesterol turnover in the mouse. J Biol Chem 277:3801\u20133804. https:\/\/doi.org\/10.1074\/jbc.R100057200","journal-title":"J Biol Chem"},{"key":"2019_CR24","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.1093\/brain\/awv166","volume":"138","author":"F Djelti","year":"2015","unstructured":"Djelti F, Braudeau J, Hudry E, Dhenain M, Varin J, Bieche I et al (2015) CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer\u2019s disease. Brain 138:2383\u20132398. https:\/\/doi.org\/10.1093\/brain\/awv166","journal-title":"Brain"},{"key":"2019_CR25","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1002\/ana.410390411","volume":"39","author":"A Durr","year":"1996","unstructured":"Durr A, Stevanin G, Cancel G, Duyckaerts C, Abbas N, Didierjean O et al (1996) Spinocerebellar ataxia 3 and Machado\u2013Joseph disease: clinical, molecular, and neuropathological features. Ann Neurol 39:490\u2013499. https:\/\/doi.org\/10.1002\/ana.410390411","journal-title":"Ann Neurol"},{"key":"2019_CR26","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/0009-3084(95)02489-6","volume":"78","author":"S Dzeletovic","year":"1995","unstructured":"Dzeletovic S, Babiker A, Lund E, Diczfalusy U (1995) Time course of oxysterol formation during in vitro oxidation of low density lipoprotein. Chem Phys Lipid 78:119\u2013128","journal-title":"Chem Phys Lipid"},{"key":"2019_CR27","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1038\/nature04724","volume":"441","author":"T Hara","year":"2006","unstructured":"Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R et al (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:885\u2013889. https:\/\/doi.org\/10.1038\/nature04724","journal-title":"Nature"},{"key":"2019_CR28","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/mt.2009.175","volume":"18","author":"E Hudry","year":"2010","unstructured":"Hudry E, Van Dam D, Kulik W, De Deyn PP, Stet FS, Ahouansou O et al (2010) Adeno-associated virus gene therapy with cholesterol 24-hydroxylase reduces the amyloid pathology before or after the onset of amyloid plaques in mouse models of Alzheimer\u2019s disease. Mol Ther 18:44\u201353. https:\/\/doi.org\/10.1038\/mt.2009.175","journal-title":"Mol Ther"},{"key":"2019_CR29","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1093\/hmg\/ddg175","volume":"12","author":"DP Huynh","year":"2003","unstructured":"Huynh DP, Yang HT, Vakharia H, Nguyen D, Pulst SM (2003) Expansion of the polyQ repeat in ataxin-2 alters its Golgi localization, disrupts the Golgi complex and causes cell death. Hum Mol Genet 12:1485\u20131496","journal-title":"Hum Mol Genet"},{"key":"2019_CR30","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/ng1194-221","volume":"8","author":"Y Kawaguchi","year":"1994","unstructured":"Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S et al (1994) CAG expansions in a novel gene for Machado\u2013Joseph disease at chromosome 14q32.1. Nat Genet 8:221\u2013228. https:\/\/doi.org\/10.1038\/ng1194-221","journal-title":"Nat Genet"},{"issue":"Pt 9","key":"2019_CR31","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1093\/brain\/121.9.1687","volume":"121","author":"T Klockgether","year":"1998","unstructured":"Klockgether T, Skalej M, Wedekind D, Luft AR, Welte D, Schulz JB et al (1998) Autosomal dominant cerebellar ataxia type I. MRI-based volumetry of posterior fossa structures and basal ganglia in spinocerebellar ataxia types 1, 2 and 3. Brain 121(Pt 9):1687\u20131693","journal-title":"Brain"},{"key":"2019_CR32","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1016\/j.neuropharm.2008.02.019","volume":"55","author":"Z Korade","year":"2008","unstructured":"Korade Z, Kenworthy AK (2008) Lipid rafts, cholesterol, and the brain. Neuropharmacology 55:1265\u20131273. https:\/\/doi.org\/10.1016\/j.neuropharm.2008.02.019","journal-title":"Neuropharmacology"},{"key":"2019_CR33","doi-asserted-by":"publisher","first-page":"3869","DOI":"10.1073\/pnas.0600316103","volume":"103","author":"TJ Kotti","year":"2006","unstructured":"Kotti TJ, Ramirez DM, Pfeiffer BE, Huber KM, Russell DW (2006) Brain cholesterol turnover required for geranylgeraniol production and learning in mice. Proc Natl Acad Sci USA 103:3869\u20133874. https:\/\/doi.org\/10.1073\/pnas.0600316103","journal-title":"Proc Natl Acad Sci USA"},{"key":"2019_CR34","doi-asserted-by":"publisher","first-page":"15055","DOI":"10.1038\/mtm.2015.55","volume":"3","author":"V Lukashchuk","year":"2016","unstructured":"Lukashchuk V, Lewis KE, Coldicott I, Grierson AJ, Azzouz M (2016) AAV9-mediated central nervous system-targeted gene delivery via cisterna magna route in mice. Mol Ther Methods Clin Dev 3:15055. https:\/\/doi.org\/10.1038\/mtm.2015.55","journal-title":"Mol Ther Methods Clin Dev"},{"key":"2019_CR35","doi-asserted-by":"publisher","first-page":"7238","DOI":"10.1073\/pnas.96.13.7238","volume":"96","author":"EG Lund","year":"1999","unstructured":"Lund EG, Guileyardo JM, Russell DW (1999) cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc Natl Acad Sci USA 96:7238\u20137243","journal-title":"Proc Natl Acad Sci USA"},{"key":"2019_CR36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303415200","author":"EG Lund","year":"2003","unstructured":"Lund EG, Xie C, Kotti T, Turley SD, Dietschy JM, Russell DW (2003) Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover. J Biol Chem. https:\/\/doi.org\/10.1074\/jbc.M303415200","journal-title":"J Biol Chem"},{"key":"2019_CR37","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/S1471-4914(01)02179-7","volume":"7","author":"RL Margolis","year":"2001","unstructured":"Margolis RL, Ross CA (2001) Expansion explosion: new clues to the pathogenesis of repeat expansion neurodegenerative diseases. Trends Mol Med 7:479\u2013482","journal-title":"Trends Mol Med"},{"key":"2019_CR38","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.15252\/embr.201439225","volume":"15","author":"MG Martin","year":"2014","unstructured":"Martin MG, Pfrieger F, Dotti CG (2014) Cholesterol in brain disease: sometimes determinant and frequently implicated. EMBO Rep 15:1036\u20131052. https:\/\/doi.org\/10.15252\/embr.201439225","journal-title":"EMBO Rep"},{"key":"2019_CR39","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s12311-013-0539-y","volume":"13","author":"A Matilla-Duenas","year":"2014","unstructured":"Matilla-Duenas A, Ashizawa T, Brice A, Magri S, McFarland KN, Pandolfo M et al (2014) Consensus paper: pathological mechanisms underlying neurodegeneration in spinocerebellar ataxias. Cerebellum 13:269\u2013302. https:\/\/doi.org\/10.1007\/s12311-013-0539-y","journal-title":"Cerebellum"},{"key":"2019_CR40","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1126\/science.294.5545.1354","volume":"294","author":"DH Mauch","year":"2001","unstructured":"Mauch DH, Nagler K, Schumacher S, Goritz C, Muller EC, Otto A et al (2001) CNS synaptogenesis promoted by glia-derived cholesterol. Science 294:1354\u20131357. https:\/\/doi.org\/10.1126\/science.294.5545.1354","journal-title":"Science"},{"key":"2019_CR41","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/S0022-2275(20)32337-3","volume":"42","author":"S Meaney","year":"2001","unstructured":"Meaney S, Hassan M, Sakinis A, Lutjohann D, von Bergmann K, Wennmalm A et al (2001) Evidence that the major oxysterols in human circulation originate from distinct pools of cholesterol: a stable isotope study. J Lipid Res 42:70\u201378","journal-title":"J Lipid Res"},{"key":"2019_CR42","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1093\/brain\/awu352","volume":"138","author":"LS Mendonca","year":"2015","unstructured":"Mendonca LS, Nobrega C, Hirai H, Kaspar BK, Pereira de Almeida L (2015) Transplantation of cerebellar neural stem cells improves motor coordination and neuropathology in Machado\u2013Joseph disease mice. Brain 138:320\u2013335. https:\/\/doi.org\/10.1093\/brain\/awu352","journal-title":"Brain"},{"key":"2019_CR43","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/nrn3961","volume":"16","author":"FM Menzies","year":"2015","unstructured":"Menzies FM, Fleming A, Rubinsztein DC (2015) Compromised autophagy and neurodegenerative diseases. Nat Rev Neurosci 16:345\u2013357. https:\/\/doi.org\/10.1038\/nrn3961","journal-title":"Nat Rev Neurosci"},{"key":"2019_CR44","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1016\/j.bbalip.2016.09.011","volume":"1861","author":"M Moutinho","year":"2016","unstructured":"Moutinho M, Nunes MJ, Rodrigues E (2016) Cholesterol 24-hydroxylase: brain cholesterol metabolism and beyond. Biochem Biophys Acta 1861:1911\u20131920. https:\/\/doi.org\/10.1016\/j.bbalip.2016.09.011","journal-title":"Biochem Biophys Acta"},{"key":"2019_CR45","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.1093\/brain\/awt144","volume":"136","author":"I Nascimento-Ferreira","year":"2013","unstructured":"Nascimento-Ferreira I, Nobrega C, Vasconcelos-Ferreira A, Onofre I, Albuquerque D, Aveleira C et al (2013) Beclin 1 mitigates motor and neuropathological deficits in genetic mouse models of Machado\u2013Joseph disease. Brain 136:2173\u20132188. https:\/\/doi.org\/10.1093\/brain\/awt144","journal-title":"Brain"},{"key":"2019_CR46","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1093\/brain\/awr047","volume":"134","author":"I Nascimento-Ferreira","year":"2011","unstructured":"Nascimento-Ferreira I, Santos-Ferreira T, Sousa-Ferreira L, Auregan G, Onofre I, Alves S et al (2011) Overexpression of the autophagic beclin-1 protein clears mutant ataxin-3 and alleviates Machado\u2013Joseph disease. Brain 134:1400\u20131415. https:\/\/doi.org\/10.1093\/brain\/awr047","journal-title":"Brain"},{"key":"2019_CR47","doi-asserted-by":"publisher","first-page":"3537","DOI":"10.1093\/brain\/awv298","volume":"138","author":"C Nobrega","year":"2015","unstructured":"Nobrega C, Carmo-Silva S, Albuquerque D, Vasconcelos-Ferreira A, Vijayakumar UG, Mendonca L et al (2015) Re-establishing ataxin-2 downregulates translation of mutant ataxin-3 and alleviates Machado\u2013Joseph disease. Brain 138:3537\u20133554. https:\/\/doi.org\/10.1093\/brain\/awv298","journal-title":"Brain"},{"key":"2019_CR48","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s12311-012-0432-0","volume":"12","author":"C Nobrega","year":"2013","unstructured":"Nobrega C, Nascimento-Ferreira I, Onofre I, Albuquerque D, Conceicao M, Deglon N et al (2013) Overexpression of mutant ataxin-3 in mouse cerebellum induces ataxia and cerebellar neuropathology. Cerebellum 12:441\u2013455. https:\/\/doi.org\/10.1007\/s12311-012-0432-0","journal-title":"Cerebellum"},{"key":"2019_CR49","doi-asserted-by":"publisher","first-page":"e100086","DOI":"10.1371\/journal.pone.0100086","volume":"9","author":"C Nobrega","year":"2014","unstructured":"Nobrega C, Nascimento-Ferreira I, Onofre I, Albuquerque D, Deglon N, de Almeida LP (2014) RNA interference mitigates motor and neuropathological deficits in a cerebellar mouse model of Machado\u2013Joseph disease. PLoS One 9:e100086. https:\/\/doi.org\/10.1371\/journal.pone.0100086","journal-title":"PLoS One"},{"key":"2019_CR50","doi-asserted-by":"publisher","first-page":"3810","DOI":"10.1074\/jbc.M505179200","volume":"281","author":"Y Ohyama","year":"2006","unstructured":"Ohyama Y, Meaney S, Heverin M, Ekstrom L, Brafman A, Shafir M et al (2006) Studies on the transcriptional regulation of cholesterol 24-hydroxylase (CYP46A1): marked insensitivity toward different regulatory axes. J Biol Chem 281:3810\u20133820. https:\/\/doi.org\/10.1074\/jbc.M505179200","journal-title":"J Biol Chem"},{"key":"2019_CR51","doi-asserted-by":"publisher","first-page":"28220","DOI":"10.1038\/srep28220","volume":"6","author":"I Onofre","year":"2016","unstructured":"Onofre I, Mendonca N, Lopes S, Nobre R, de Melo JB, Carreira IM et al (2016) Fibroblasts of Machado\u2013Joseph disease patients reveal autophagy impairment. Sci Rep 6:28220. https:\/\/doi.org\/10.1038\/srep28220","journal-title":"Sci Rep"},{"key":"2019_CR52","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1146\/annurev.neuro.29.051605.113042","volume":"30","author":"HT Orr","year":"2007","unstructured":"Orr HT, Zoghbi HY (2007) Trinucleotide repeat disorders. Annu Rev Neurosci 30:575\u2013621. https:\/\/doi.org\/10.1146\/annurev.neuro.29.051605.113042","journal-title":"Annu Rev Neurosci"},{"key":"2019_CR53","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.brainres.2008.12.014","volume":"1255","author":"M Oue","year":"2009","unstructured":"Oue M, Mitsumura K, Torashima T, Koyama C, Yamaguchi H, Furuya N et al (2009) Characterization of mutant mice that express polyglutamine in cerebellar Purkinje cells. Brain Res 1255:9\u201317. https:\/\/doi.org\/10.1016\/j.brainres.2008.12.014","journal-title":"Brain Res"},{"key":"2019_CR54","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1002\/cne.21605","volume":"507","author":"DM Ramirez","year":"2008","unstructured":"Ramirez DM, Andersson S, Russell DW (2008) Neuronal expression and subcellular localization of cholesterol 24-hydroxylase in the mouse brain. J Comp Neurol 507:1676\u20131693. https:\/\/doi.org\/10.1002\/cne.21605","journal-title":"J Comp Neurol"},{"key":"2019_CR55","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1093\/brain\/aws369","volume":"136","author":"K Reetz","year":"2013","unstructured":"Reetz K, Costa AS, Mirzazade S, Lehmann A, Juzek A, Rakowicz M et al (2013) Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6. Brain 136:905\u2013917. https:\/\/doi.org\/10.1093\/brain\/aws369","journal-title":"Brain"},{"key":"2019_CR56","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1097\/WCO.0b013e3282f7673d","volume":"21","author":"U Rub","year":"2008","unstructured":"Rub U, Brunt ER, Deller T (2008) New insights into the pathoanatomy of spinocerebellar ataxia type 3 (Machado\u2013Joseph disease). Curr Opin Neurol 21:111\u2013116. https:\/\/doi.org\/10.1097\/WCO.0b013e3282f7673d","journal-title":"Curr Opin Neurol"},{"key":"2019_CR57","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1111\/j.1365-2990.2006.00772.x","volume":"32","author":"U Rub","year":"2006","unstructured":"Rub U, Brunt ER, Petrasch-Parwez E, Schols L, Theegarten D, Auburger G et al (2006) Degeneration of ingestion-related brainstem nuclei in spinocerebellar ataxia type 2, 3, 6 and 7. Neuropathol Appl Neurobiol 32:635\u2013649. https:\/\/doi.org\/10.1111\/j.1365-2990.2006.00772.x","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2019_CR58","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1146\/annurev.biochem.78.072407.103859","volume":"78","author":"DW Russell","year":"2009","unstructured":"Russell DW, Halford RW, Ramirez DM, Shah R, Kotti T (2009) Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain. Annu Rev Biochem 78:1017\u20131040. https:\/\/doi.org\/10.1146\/annurev.biochem.78.072407.103859","journal-title":"Annu Rev Biochem"},{"key":"2019_CR59","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1089\/hum.2011.200","volume":"23","author":"L Samaranch","year":"2012","unstructured":"Samaranch L, Salegio EA, San Sebastian W, Kells AP, Foust KD, Bringas JR et al (2012) Adeno-associated virus serotype 9 transduction in the central nervous system of nonhuman primates. Hum Gene Ther 23:382\u2013389. https:\/\/doi.org\/10.1089\/hum.2011.200","journal-title":"Hum Gene Ther"},{"key":"2019_CR60","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1007\/s12311-011-0340-8","volume":"11","author":"W Scherzed","year":"2012","unstructured":"Scherzed W, Brunt ER, Heinsen H, de Vos RA, Seidel K, Burk K et al (2012) Pathoanatomy of cerebellar degeneration in spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3). Cerebellum 11:749\u2013760. https:\/\/doi.org\/10.1007\/s12311-011-0340-8","journal-title":"Cerebellum"},{"key":"2019_CR61","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1002\/ana.410420615","volume":"42","author":"L Schols","year":"1997","unstructured":"Schols L, Amoiridis G, Buttner T, Przuntek H, Epplen JT, Riess O (1997) Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes? Ann Neurol 42:924\u2013932. https:\/\/doi.org\/10.1002\/ana.410420615","journal-title":"Ann Neurol"},{"key":"2019_CR62","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/S1474-4422(04)00737-9","volume":"3","author":"L Schols","year":"2004","unstructured":"Schols L, Bauer P, Schmidt T, Schulte T, Riess O (2004) Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol 3:291\u2013304. https:\/\/doi.org\/10.1016\/S1474-4422(04)00737-9","journal-title":"Lancet Neurol"},{"key":"2019_CR63","doi-asserted-by":"publisher","first-page":"42","DOI":"10.3389\/fnana.2014.00042","volume":"8","author":"DJ Schuster","year":"2014","unstructured":"Schuster DJ, Dykstra JA, Riedl MS, Kitto KF, Belur LR, McIvor RS et al (2014) Biodistribution of adeno-associated virus serotype 9 (AAV9) vector after intrathecal and intravenous delivery in mouse. Front Neuroanat 8:42. https:\/\/doi.org\/10.3389\/fnana.2014.00042","journal-title":"Front Neuroanat"},{"key":"2019_CR64","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12433","author":"A Sittler","year":"2017","unstructured":"Sittler A, Muriel MP, Marinello M, Brice A, den Dunnen W, Alves S (2017) Deregulation of autophagy in postmortem brains of Machado\u2013Joseph disease patients. Neuropathology. https:\/\/doi.org\/10.1111\/neup.12433","journal-title":"Neuropathology"},{"key":"2019_CR65","doi-asserted-by":"publisher","first-page":"e851","DOI":"10.1371\/journal.pone.0000851","volume":"2","author":"K Sobo","year":"2007","unstructured":"Sobo K, Le Blanc I, Luyet PP, Fivaz M, Ferguson C, Parton RG et al (2007) Late endosomal cholesterol accumulation leads to impaired intra-endosomal trafficking. PLoS One 2:e851. https:\/\/doi.org\/10.1371\/journal.pone.0000851","journal-title":"PLoS One"},{"key":"2019_CR66","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1111\/j.1471-4159.2010.07079.x","volume":"116","author":"AO Sodero","year":"2011","unstructured":"Sodero AO, Trovo L, Iannilli F, Van Veldhoven P, Dotti CG, Martin MG (2011) Regulation of tyrosine kinase B activity by the Cyp46\/cholesterol loss pathway in mature hippocampal neurons: relevance for neuronal survival under stress and in aging. J Neurochem 116:747\u2013755. https:\/\/doi.org\/10.1111\/j.1471-4159.2010.07079.x","journal-title":"J Neurochem"},{"key":"2019_CR67","doi-asserted-by":"publisher","first-page":"1764","DOI":"10.1038\/emboj.2012.31","volume":"31","author":"AO Sodero","year":"2012","unstructured":"Sodero AO, Vriens J, Ghosh D, Stegner D, Brachet A, Pallotto M et al (2012) Cholesterol loss during glutamate-mediated excitotoxicity. EMBO J 31:1764\u20131773. https:\/\/doi.org\/10.1038\/emboj.2012.31","journal-title":"EMBO J"},{"key":"2019_CR68","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1093\/brain\/awv064","volume":"138","author":"MR Stefanescu","year":"2015","unstructured":"Stefanescu MR, Dohnalek M, Maderwald S, Thurling M, Minnerop M, Beck A et al (2015) Structural and functional MRI abnormalities of cerebellar cortex and nuclei in SCA3, SCA6 and Friedreich\u2019s ataxia. Brain 138:1182\u20131197. https:\/\/doi.org\/10.1093\/brain\/awv064","journal-title":"Brain"},{"key":"2019_CR69","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.neulet.2006.04.034","volume":"403","author":"KM Thelen","year":"2006","unstructured":"Thelen KM, Falkai P, Bayer TA, Lutjohann D (2006) Cholesterol synthesis rate in human hippocampus declines with aging. Neurosci Lett 403:15\u201319. https:\/\/doi.org\/10.1016\/j.neulet.2006.04.034","journal-title":"Neurosci Lett"},{"key":"2019_CR70","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13024-018-0261-9","volume":"13","author":"LJA Toonen","year":"2018","unstructured":"Toonen LJA, Overzier M, Evers MM, Leon LG, van der Zeeuw SAJ, Mei H et al (2018) Transcriptional profiling and biomarker identification reveal tissue specific effects of expanded ataxin-3 in a spinocerebellar ataxia type 3 mouse model. Mol Neurodegener 13:31. https:\/\/doi.org\/10.1186\/s13024-018-0261-9","journal-title":"Mol Neurodegener"},{"key":"2019_CR71","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/embor.2008.31","volume":"9","author":"T Torashima","year":"2008","unstructured":"Torashima T, Koyama C, Iizuka A, Mitsumura K, Takayama K, Yanagi S et al (2008) Lentivector-mediated rescue from cerebellar ataxia in a mouse model of spinocerebellar ataxia. EMBO Rep 9:393\u2013399. https:\/\/doi.org\/10.1038\/embor.2008.31","journal-title":"EMBO Rep"},{"key":"2019_CR72","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1242\/dmm.010124","volume":"5","author":"JE Vance","year":"2012","unstructured":"Vance JE (2012) Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases. Dis Models Mech 5:746\u2013755. https:\/\/doi.org\/10.1242\/dmm.010124","journal-title":"Dis Models Mech"},{"key":"2019_CR73","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1089\/humc.2014.139","volume":"26","author":"M Zerah","year":"2015","unstructured":"Zerah M, Piguet F, Colle MA, Raoul S, Deschamps JY, Deniaud J et al (2015) Intracerebral gene therapy using AAVrh. 10-hARSA recombinant vector to treat patients with early-onset forms of metachromatic leukodystrophy: preclinical feasibility and safety assessments in nonhuman primates. Hum Gene Ther Clin Dev 26:113\u2013124. https:\/\/doi.org\/10.1089\/humc.2014.139","journal-title":"Hum Gene Ther Clin Dev"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-019-02019-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00401-019-02019-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-019-02019-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T15:17:05Z","timestamp":1663687025000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00401-019-02019-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,14]]},"references-count":73,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["2019"],"URL":"https:\/\/doi.org\/10.1007\/s00401-019-02019-7","relation":{},"ISSN":["0001-6322","1432-0533"],"issn-type":[{"value":"0001-6322","type":"print"},{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,14]]},"assertion":[{"value":"2 October 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 April 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare financial interest. CN, LM, NC, LPA and SA are inventors of patent applications claiming the use of AAV-CYP46A1 therapy in spinocerebellar ataxias.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}