{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:45:15Z","timestamp":1790779515867,"version":"4.1.0"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2015,11,20]],"date-time":"2015-11-20T00:00:00Z","timestamp":1447977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2015,11,20]],"date-time":"2015-11-20T00:00:00Z","timestamp":1447977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Neuromics European","award":["305121"],"award-info":[{"award-number":["305121"]}]},{"name":"Ministero della Salute under 40","award":["GR\u20102008\u20101145270"],"award-info":[{"award-number":["GR\u20102008\u20101145270"]}]},{"DOI":"10.13039\/100007197","name":"USPHS","doi-asserted-by":"crossref","award":["NS41574"],"award-info":[{"award-number":["NS41574"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007197","name":"USPHS","doi-asserted-by":"crossref","award":["HD004612"],"award-info":[{"award-number":["HD004612"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007197","name":"USPHS","doi-asserted-by":"crossref","award":["NS081335"],"award-info":[{"award-number":["NS081335"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001671","name":"The Hereditary Disease Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001671","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2015,12,1]]},"DOI":"10.15252\/emmm.201505413","type":"journal-article","created":{"date-parts":[[2015,11,20]],"date-time":"2015-11-20T21:39:14Z","timestamp":1448055554000},"page":"1547-1564","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Cholesterol\u2010loaded nanoparticles ameliorate synaptic and cognitive function in Huntington's disease mice"],"prefix":"10.1038","volume":"7","author":[{"given":"Marta","family":"Valenza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane Y","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Di Paolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Ruozi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Belletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costanza","family":"Ferrari Bardile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Leoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Caccia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Brilli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Di Donato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina M","family":"Boido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Vercelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A","family":"Vandelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Forni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Cepeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S","family":"Levine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Tosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Cattaneo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,11,20]]},"reference":[{"key":"BFEMMM201505413_CR1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jconrel.2012.03.020","volume":"160","author":"Y Barenholz","year":"2012","unstructured":"Barenholz Y (2012) Doxil(R)\u2013the first FDA\u2010approved nano\u2010drug: lessons learned. J Control Release 160: 117\u2013134","journal-title":"J Control Release"},{"key":"BFEMMM201505413_CR2","doi-asserted-by":"crossref","first-page":"10721","DOI":"10.1523\/JNEUROSCI.6413-10.2011","volume":"31","author":"GR Barker","year":"2011","unstructured":"Barker GR, Warburton EC (2011) When is the hippocampus involved in recognition memory? J Neurosci 31: 10721\u201310731","journal-title":"J Neurosci"},{"key":"BFEMMM201505413_CR3","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.ijpharm.2012.07.070","volume":"436","author":"D Belletti","year":"2012","unstructured":"Belletti D, Tosi G, Forni F, Gamberini MC, Baraldi C, Vandelli MA, Ruozi B (2012) Chemico\u2010physical investigation of tenofovir loaded polymeric nanoparticles. Int J Pharm 436: 753\u2013763","journal-title":"Int J Pharm"},{"key":"BFEMMM201505413_CR4","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1523\/JNEUROSCI.23-03-00961.2003","volume":"23","author":"C Cepeda","year":"2003","unstructured":"Cepeda C, Hurst RS, Calvert CR, Hernandez\u2010Echeagaray E, Nguyen OK, Jocoy E, Christian LJ, Ariano MA, Levine MS (2003) Transient and progressive electrophysiological alterations in the corticostriatal pathway in a mouse model of Huntington's disease. J Neurosci 23: 961\u2013969","journal-title":"J Neurosci"},{"key":"BFEMMM201505413_CR5","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1002\/jnr.20344","volume":"78","author":"C Cepeda","year":"2004","unstructured":"Cepeda C, Starling AJ, Wu N, Nguyen OK, Uzgil B, Soda T, Andre VM, Ariano MA, Levine MS (2004) Increased GABAergic function in mouse models of Huntington's disease: reversal by BDNF. J Neurosci Res 78: 855\u2013867","journal-title":"J Neurosci Res"},{"key":"BFEMMM201505413_CR6","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.bbi.2014.09.011","volume":"44","author":"KH Chang","year":"2015","unstructured":"Chang KH, Wu YR, Chen YC, Chen CM (2015) Plasma inflammatory biomarkers for Huntington's disease patients and mouse model. Brain Behav Immun 44: 121\u2013127","journal-title":"Brain Behav Immun"},{"key":"BFEMMM201505413_CR7","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.nbd.2012.10.015","volume":"50","author":"P Conforti","year":"2013","unstructured":"Conforti P, Camnasio S, Mutti C, Valenza M, Thompson M, Fossale E, Zeitlin S, MacDonald ME, Zuccato C, Cattaneo E (2013) Lack of huntingtin promotes neural stem cells differentiation into glial cells while neurons expressing huntingtin with expanded polyglutamine tracts undergo cell death. Neurobiol Dis 50: 160\u2013170","journal-title":"Neurobiol Dis"},{"key":"BFEMMM201505413_CR8","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jconrel.2005.07.013","volume":"108","author":"L Costantino","year":"2005","unstructured":"Costantino L, Gandolfi F, Tosi G, Rivasi F, Vandelli MA, Forni F (2005) Peptide\u2010derivatized biodegradable nanoparticles able to cross the blood\u2010brain barrier. J Control Release 108: 84\u201396","journal-title":"J Control Release"},{"key":"BFEMMM201505413_CR9","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1093\/hmg\/ddl224","volume":"15","author":"DM Cummings","year":"2006","unstructured":"Cummings DM, Milnerwood AJ, Dallerac GM, Waights V, Brown JY, Vatsavayai SC, Hirst MC, Murphy KP (2006) Aberrant cortical synaptic plasticity and dopaminergic dysfunction in a mouse model of Huntington's disease. Hum Mol Genet 15: 2856\u20132868","journal-title":"Hum Mol Genet"},{"key":"BFEMMM201505413_CR10","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.jconrel.2012.01.043","volume":"161","author":"F Danhier","year":"2012","unstructured":"Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Preat V (2012) PLGA\u2010based nanoparticles: an overview of biomedical applications. J Control Release 161: 505\u2013522","journal-title":"J Control Release"},{"key":"BFEMMM201505413_CR11","doi-asserted-by":"crossref","first-page":"14664","DOI":"10.1073\/pnas.0907299106","volume":"106","author":"M Darvas","year":"2009","unstructured":"Darvas M, Palmiter RD (2009) Restriction of dopamine signaling to the dorsolateral striatum is sufficient for many cognitive behaviors. Proc Natl Acad Sci USA 106: 14664\u201314669","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM201505413_CR12","doi-asserted-by":"crossref","first-page":"15856","DOI":"10.1523\/JNEUROSCI.4132-10.2010","volume":"30","author":"JS Dason","year":"2010","unstructured":"Dason JS, Smith AJ, Marin L, Charlton MP (2010) Vesicular sterols are essential for synaptic vesicle cycling. J Neurosci 30: 15856\u201315865","journal-title":"J Neurosci"},{"key":"BFEMMM201505413_CR13","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1113\/jphysiol.2013.265447","volume":"592","author":"JS Dason","year":"2014","unstructured":"Dason JS, Smith AJ, Marin L, Charlton MP (2014) Cholesterol and F\u2010actin are required for clustering of recycling synaptic vesicle proteins in the presynaptic plasma membrane. J Physiol 592: 621\u2013633","journal-title":"J Physiol"},{"key":"BFEMMM201505413_CR14","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1194\/jlr.R400004-JLR200","volume":"45","author":"JM Dietschy","year":"2004","unstructured":"Dietschy JM, Turley SD (2004) Thematic review series: brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J Lipid Res 45: 1375\u20131397","journal-title":"J Lipid Res"},{"key":"BFEMMM201505413_CR15","first-page":"25","volume":"566","author":"C Frank","year":"2004","unstructured":"Frank C, Giammarioli AM, Pepponi R, Fiorentini C, Rufini S (2004) Cholesterol perturbing agents inhibit NMDA\u2010dependent calcium influx in rat hippocampal primary culture. FEBS Lett 566: 25\u201329","journal-title":"FEBS Lett"},{"key":"BFEMMM201505413_CR16","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.expneurol.2008.04.019","volume":"212","author":"C Frank","year":"2008","unstructured":"Frank C, Rufini S, Tancredi V, Forcina R, Grossi D, D'Arcangelo G (2008) Cholesterol depletion inhibits synaptic transmission and synaptic plasticity in rat hippocampus. Exp Neurol 212: 407\u2013414","journal-title":"Exp Neurol"},{"key":"BFEMMM201505413_CR17","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.brainresbull.2003.12.004","volume":"63","author":"W Freeman","year":"2004","unstructured":"Freeman W, Morton AJ (2004) Regional and progressive changes in brain expression of complexin II in a mouse transgenic for the Huntington's disease mutation. Brain Res Bull 63: 45\u201355","journal-title":"Brain Res Bull"},{"key":"BFEMMM201505413_CR18","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.nbd.2009.07.028","volume":"37","author":"R Gabathuler","year":"2010","unstructured":"Gabathuler R (2010) Approaches to transport therapeutic drugs across the blood\u2010brain barrier to treat brain diseases. Neurobiol Dis 37: 48\u201357","journal-title":"Neurobiol Dis"},{"key":"BFEMMM201505413_CR19","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1523\/JNEUROSCI.3921-08.2009","volume":"29","author":"F Gardoni","year":"2009","unstructured":"Gardoni F, Mauceri D, Malinverno M, Polli F, Costa C, Tozzi A, Siliquini S, Picconi B, Cattabeni F, Calabresi P et\u00a0al (2009) Decreased NR2B subunit synaptic levels cause impaired long\u2010term potentiation but not long\u2010term depression. J Neurosci 29: 669\u2013677","journal-title":"J Neurosci"},{"key":"BFEMMM201505413_CR20","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s10540-007-9060-1","volume":"27","author":"G Gimpl","year":"2007","unstructured":"Gimpl G, Gehrig\u2010Burger K (2007) Cholesterol reporter molecules. Biosci Rep 27: 335\u2013358","journal-title":"Biosci Rep"},{"key":"BFEMMM201505413_CR21","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1093\/hmg\/ddg249","volume":"12","author":"D Glynn","year":"2003","unstructured":"Glynn D, Bortnick RA, Morton AJ (2003) Complexin II is essential for normal neurological function in mice. Hum Mol Genet 12: 2431\u20132448","journal-title":"Hum Mol Genet"},{"key":"BFEMMM201505413_CR22","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1097\/01.WCB.0000135592.28823.47","volume":"24","author":"S Gosk","year":"2004","unstructured":"Gosk S, Vermehren C, Storm G, Moos T (2004) Targeting anti\u2010transferrin receptor antibody (OX26) and OX26\u2010conjugated liposomes to brain capillary endothelial cells using in\u00a0situ perfusion. J Cereb Blood Flow Metab 24: 1193\u20131204","journal-title":"J Cereb Blood Flow Metab"},{"key":"BFEMMM201505413_CR23","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1152\/physrev.00036.2014","volume":"95","author":"Y Hara","year":"2015","unstructured":"Hara Y, Waters EM, McEwen BS, Morrison JH (2015) Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse. Physiol Rev 95: 785\u2013807","journal-title":"Physiol Rev"},{"key":"BFEMMM201505413_CR24","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","volume":"72","author":"HDCRG","year":"1993","unstructured":"HDCRG (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell 72: 971\u2013983","journal-title":"Cell"},{"key":"BFEMMM201505413_CR25","doi-asserted-by":"crossref","first-page":"3262","DOI":"10.1523\/JNEUROSCI.23-08-03262.2003","volume":"23","author":"H Hering","year":"2003","unstructured":"Hering H, Lin CC, Sheng M (2003) Lipid rafts in the maintenance of synapses, dendritic spines, and surface AMPA receptor stability. J Neurosci 23: 3262\u20133271","journal-title":"J Neurosci"},{"key":"BFEMMM201505413_CR26","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/S0955-0674(00)00239-8","volume":"13","author":"WB Huttner","year":"2001","unstructured":"Huttner WB, Zimmerberg J (2001) Implications of lipid microdomains for membrane curvature, budding and fission. Curr Opin Cell Biol 13: 478\u2013484","journal-title":"Curr Opin Cell Biol"},{"key":"BFEMMM201505413_CR27","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1523\/JNEUROSCI.5687-08.2009","volume":"29","author":"PR Joshi","year":"2009","unstructured":"Joshi PR, Wu NP, Andre VM, Cummings DM, Cepeda C, Joyce JA, Carroll JB, Leavitt BR, Hayden MR, Levine MS et\u00a0al (2009) Age\u2010dependent alterations of corticostriatal activity in the YAC128 mouse model of Huntington disease. J Neurosci 29: 2414\u20132427","journal-title":"J Neurosci"},{"key":"BFEMMM201505413_CR28","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1093\/emboj\/20.9.2202","volume":"20","author":"T Lang","year":"2001","unstructured":"Lang T, Bruns D, Wenzel D, Riedel D, Holroyd P, Thiele C, Jahn R (2001) SNAREs are concentrated in cholesterol\u2010dependent clusters that define docking and fusion sites for exocytosis. EMBO J 20: 2202\u20132213","journal-title":"EMBO J"},{"issue":"Pt 5","key":"BFEMMM201505413_CR29","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1093\/brain\/119.5.1633","volume":"119","author":"AD Lawrence","year":"1996","unstructured":"Lawrence AD, Sahakian BJ, Hodges JR, Rosser AE, Lange KW, Robbins TW (1996) Executive and mnemonic functions in early Huntington's disease. Brain 119(Pt 5): 1633\u20131645","journal-title":"Brain"},{"issue":"Pt 7","key":"BFEMMM201505413_CR30","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1093\/brain\/123.7.1349","volume":"123","author":"AD Lawrence","year":"2000","unstructured":"Lawrence AD, Watkins LH, Sahakian BJ, Hodges JR, Robbins TW (2000) Visual object and visuospatial cognition in Huntington's disease: implications for information processing in corticostriatal circuits. Brain 123(Pt 7): 1349\u20131364","journal-title":"Brain"},{"key":"BFEMMM201505413_CR31","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1093\/brain\/awn212","volume":"131","author":"V Leoni","year":"2008","unstructured":"Leoni V, Mariotti C, Tabrizi SJ, Valenza M, Wild EJ, Henley SM, Hobbs NZ, Mandelli ML, Grisoli M, Bjorkhem I et\u00a0al (2008) Plasma 24S\u2010hydroxycholesterol and caudate MRI in pre\u2010manifest and early Huntington's disease. Brain 131: 2851\u20132859","journal-title":"Brain"},{"key":"BFEMMM201505413_CR32","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.nbd.2013.03.013","volume":"55","author":"V Leoni","year":"2013","unstructured":"Leoni V, Long JD, Mills JA, Di Donato S, Paulsen JS, Group P\u2010Hs (2013) Plasma 24S\u2010hydroxycholesterol correlation with markers of Huntington disease progression. Neurobiol Dis 55: 37\u201343","journal-title":"Neurobiol Dis"},{"key":"BFEMMM201505413_CR33","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.tins.2004.08.008","volume":"27","author":"MS Levine","year":"2004","unstructured":"Levine MS, Cepeda C, Hickey MA, Fleming SM, Chesselet MF (2004) Genetic mouse models of Huntington's and Parkinson's diseases: illuminating but imperfect. Trends Neurosci 27: 691\u2013697","journal-title":"Trends Neurosci"},{"key":"BFEMMM201505413_CR34","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1242\/jcs.060681","volume":"123","author":"A Linetti","year":"2010","unstructured":"Linetti A, Fratangeli A, Taverna E, Valnegri P, Francolini M, Cappello V, Matteoli M, Passafaro M, Rosa P (2010) Cholesterol reduction impairs exocytosis of synaptic vesicles. J Cell Sci 123: 595\u2013605","journal-title":"J Cell Sci"},{"key":"BFEMMM201505413_CR35","doi-asserted-by":"crossref","first-page":"22980","DOI":"10.1074\/jbc.M303415200","volume":"278","author":"EG Lund","year":"2003","unstructured":"Lund EG, Xie C, Kotti T, Turley SD, Dietschy JM, Russell DW (2003) Knockout of the cholesterol 24\u2010hydroxylase gene in mice reveals a brain\u2010specific mechanism of cholesterol turnover. J Biol Chem 278: 22980\u201322988","journal-title":"J Biol Chem"},{"key":"BFEMMM201505413_CR36","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0092-8674(00)81369-0","volume":"87","author":"L Mangiarini","year":"1996","unstructured":"Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, Lawton M, Trottier Y, Lehrach H, Davies SW et\u00a0al (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87: 493\u2013506","journal-title":"Cell"},{"key":"BFEMMM201505413_CR37","doi-asserted-by":"crossref","first-page":"902","DOI":"10.15252\/emmm.201303711","volume":"6","author":"MG Martin","year":"2014","unstructured":"Martin MG, Ahmed T, Korovaichuk A, Venero C, Menchon SA, Salas I, Munck S, Herreras O, Balschun D, Dotti CG (2014a) Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents. EMBO Mol Med 6: 902\u2013917","journal-title":"EMBO Mol Med"},{"key":"BFEMMM201505413_CR38","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.15252\/embr.201439225","volume":"15","author":"MG Martin","year":"2014","unstructured":"Martin MG, Pfrieger F, Dotti CG (2014b) Cholesterol in brain disease: sometimes determinant and frequently implicated. EMBO Rep 15: 1036\u20131052","journal-title":"EMBO Rep"},{"key":"BFEMMM201505413_CR39","first-page":"e505886e505889a","volume":"4","author":"M Marullo","year":"2012","unstructured":"Marullo M, Valenza M, Leoni V, Caccia C, Scarlatti C, De MA, Zuccato C, Di Donato S, Carafoli E, Cattaneo E (2012) Pitfalls in the detection of cholesterol in Huntington's disease models. PLoS Curr 4: e505886e505889a501968","journal-title":"PLoS Curr"},{"key":"BFEMMM201505413_CR40","doi-asserted-by":"crossref","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, Pfrieger FW (2001) CNS synaptogenesis promoted by glia\u2010derived cholesterol. Science 294: 1354\u20131357","journal-title":"Science"},{"key":"BFEMMM201505413_CR41","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neuron.2010.01.008","volume":"65","author":"AJ Milnerwood","year":"2010","unstructured":"Milnerwood AJ, Gladding CM, Pouladi MA, Kaufman AM, Hines RM, Boyd JD, Ko RW, Vasuta OC, Graham RK, Hayden MR et\u00a0al (2010) Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice. Neuron 65: 178\u2013190","journal-title":"Neuron"},{"key":"BFEMMM201505413_CR42","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.tins.2010.08.002","volume":"33","author":"AJ Milnerwood","year":"2010","unstructured":"Milnerwood AJ, Raymond LA (2010) Early synaptic pathophysiology in neurodegeneration: insights from Huntington's disease. Trends Neurosci 33: 513\u2013523","journal-title":"Trends Neurosci"},{"key":"BFEMMM201505413_CR43","doi-asserted-by":"crossref","first-page":"250","DOI":"10.2174\/187221112802652615","volume":"6","author":"A Minost","year":"2012","unstructured":"Minost A, Delaveau J, Bolzinger MA, Fessi H, Elaissari A (2012) Nanoparticles via nanoprecipitation process. Recent Pat Drug Deliv Formul 6: 250\u2013258","journal-title":"Recent Pat Drug Deliv Formul"},{"key":"BFEMMM201505413_CR44","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1046\/j.1471-4159.2001.00059.x","volume":"76","author":"AJ Morton","year":"2001","unstructured":"Morton AJ, Edwardson JM (2001) Progressive depletion of complexin II in a transgenic mouse model of Huntington's disease. J Neurochem 76: 166\u2013172","journal-title":"J Neurochem"},{"key":"BFEMMM201505413_CR45","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jconrel.2007.09.013","volume":"125","author":"RC Mundargi","year":"2008","unstructured":"Mundargi RC, Babu VR, Rangaswamy V, Patel P, Aminabhavi TM (2008) Nano\/micro technologies for delivering macromolecular therapeutics using poly(D, L\u2010lactide\u2010co\u2010glycolide) and its derivatives. J Control Release 125: 193\u2013209","journal-title":"J Control Release"},{"key":"BFEMMM201505413_CR46","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1136\/jnnp.2009.171926","volume":"81","author":"M Orth","year":"2010","unstructured":"Orth M, Schippling S, Schneider SA, Bhatia KP, Talelli P, Tabrizi SJ, Rothwell JC (2010) Abnormal motor cortex plasticity in premanifest and very early manifest Huntington disease. J Neurol Neurosurg Psychiatry 81: 267\u2013270","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"BFEMMM201505413_CR47","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/S0959-4388(02)00363-X","volume":"12","author":"G Paratcha","year":"2002","unstructured":"Paratcha G, Ibanez CF (2002) Lipid rafts and the control of neurotrophic factor signaling in the nervous system: variations on a theme. Curr Opin Neurobiol 12: 542\u2013549","journal-title":"Curr Opin Neurobiol"},{"key":"BFEMMM201505413_CR48","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1136\/jnnp.2007.128728","volume":"79","author":"JS Paulsen","year":"2008","unstructured":"Paulsen JS, Langbehn DR, Stout JC, Aylward E, Ross CA, Nance M, Guttman M, Johnson S, MacDonald M, Beglinger LJ et\u00a0al (2008) Detection of Huntington's disease decades before diagnosis: the Predict\u2010HD study. J Neurol Neurosurg Psychiatry 79: 874\u2013880","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"BFEMMM201505413_CR49","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1002\/mds.25997","volume":"29","author":"JS Paulsen","year":"2014","unstructured":"Paulsen JS, Long JD (2014) Onset of Huntington's disease: can it be purely cognitive? Mov Disord 29: 1342\u20131350","journal-title":"Mov Disord"},{"key":"BFEMMM201505413_CR500","volume-title":"Paxinos and Franklin's the Mouse Brain in Stereotaxic Coordinates","author":"G Paxinos","year":"2008","unstructured":"Paxinos G, Franklin KBJ (2008) Paxinos and Franklin's the Mouse Brain in Stereotaxic Coordinates, 3rd edn. Waltham, MA: Academic Press","edition":"3rd edn"},{"key":"BFEMMM201505413_CR50","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0005-2736(03)00024-5","volume":"1610","author":"FW Pfrieger","year":"2003","unstructured":"Pfrieger FW (2003) Role of cholesterol in synapse formation and function. Biochim Biophys Acta 1610: 271\u2013280","journal-title":"Biochim Biophys Acta"},{"key":"BFEMMM201505413_CR51","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0092-8674(01)00192-1","volume":"104","author":"K Reim","year":"2001","unstructured":"Reim K, Mansour M, Varoqueaux F, McMahon HT, Sudhof TC, Brose N, Rosenmund C (2001) Complexins regulate a late step in Ca2\u00a0+\u00a0\u2010dependent neurotransmitter release. Cell 104: 71\u201381","journal-title":"Cell"},{"key":"BFEMMM201505413_CR52","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1523\/JNEUROSCI.4445-08.2009","volume":"29","author":"M Renner","year":"2009","unstructured":"Renner M, Choquet D, Triller A (2009) Control of the postsynaptic membrane viscosity. J Neurosci 29: 2926\u20132937","journal-title":"J Neurosci"},{"key":"BFEMMM201505413_CR53","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nrneurol.2014.24","volume":"10","author":"CA Ross","year":"2014","unstructured":"Ross CA, Aylward EH, Wild EJ, Langbehn DR, Long JD, Warner JH, Scahill RI, Leavitt BR, Stout JC, Paulsen JS et\u00a0al (2014) Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol 10: 204\u2013216","journal-title":"Nat Rev Neurol"},{"key":"BFEMMM201505413_CR54","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.biopsych.2008.12.026","volume":"65","author":"S Schippling","year":"2009","unstructured":"Schippling S, Schneider SA, Bhatia KP, Munchau A, Rothwell JC, Tabrizi SJ, Orth M (2009) Abnormal motor cortex excitability in preclinical and very early Huntington's disease. Biol Psychiatry 65: 959\u2013965","journal-title":"Biol Psychiatry"},{"key":"BFEMMM201505413_CR55","first-page":"597","volume":"70","author":"A Sethi","year":"2013","unstructured":"Sethi A, Sher M, Akram MR, Karim S, Khiljee S, Sajjad A, Shah SN, Murtaza G (2013) Albumin as a drug delivery and diagnostic tool and its market approved products. Acta Pol Pharm 70: 597\u2013600","journal-title":"Acta Pol Pharm"},{"key":"BFEMMM201505413_CR56","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1158\/1078-0432.CCR-12-2764","volume":"19","author":"H Shen","year":"2013","unstructured":"Shen H, Rodriguez\u2010Aguayo C, Xu R, Gonzalez\u2010Villasana V, Mai J, Huang Y, Zhang G, Guo X, Bai L, Qin G et\u00a0al (2013) Enhancing chemotherapy response with sustained EphA2 silencing using multistage vector delivery. Clin Cancer Res 19: 1806\u20131815","journal-title":"Clin Cancer Res"},{"key":"BFEMMM201505413_CR57","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0169-409X(97)00048-3","volume":"28","author":"MS Shive","year":"1997","unstructured":"Shive MS, Anderson JM (1997) Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev 28: 5\u201324","journal-title":"Adv Drug Deliv Rev"},{"key":"BFEMMM201505413_CR58","doi-asserted-by":"crossref","first-page":"e1001532","DOI":"10.1371\/journal.pbio.1001532","volume":"11","author":"R Suzuki","year":"2013","unstructured":"Suzuki R, Ferris HA, Chee MJ, Maratos\u2010Flier E, Kahn CR (2013) Reduction of the cholesterol sensor SCAP in the brains of mice causes impaired synaptic transmission and altered cognitive function. PLoS Biol 11: e1001532","journal-title":"PLoS Biol"},{"key":"BFEMMM201505413_CR59","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/nnano.2008.34","volume":"3","author":"E Tasciotti","year":"2008","unstructured":"Tasciotti E, Liu X, Bhavane R, Plant K, Leonard AD, Price BK, Cheng MM, Decuzzi P, Tour JM, Robertson F et\u00a0al (2008) Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nat Nanotechnol 3: 151\u2013157","journal-title":"Nat Nanotechnol"},{"key":"BFEMMM201505413_CR60","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/71366","volume":"2","author":"C Thiele","year":"2000","unstructured":"Thiele C, Hannah MJ, Fahrenholz F, Huttner WB (2000) Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles. Nat Cell Biol 2: 42\u201349","journal-title":"Nat Cell Biol"},{"key":"BFEMMM201505413_CR61","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1471-4159.2010.06912.x","volume":"115","author":"D del Toro","year":"2010","unstructured":"del Toro D, Xifro X, Pol A, Humbert S, Saudou F, Canals JM, Alberch J (2010) Altered cholesterol homeostasis contributes to enhanced excitotoxicity in Huntington's disease. J Neurochem 115: 153\u2013167","journal-title":"J Neurochem"},{"key":"BFEMMM201505413_CR62","doi-asserted-by":"crossref","first-page":"4189","DOI":"10.1016\/j.biomaterials.2004.10.025","volume":"26","author":"G Tosi","year":"2005","unstructured":"Tosi G, Rivasi F, Gandolfi F, Costantino L, Vandelli MA, Forni F (2005) Conjugated poly(D, L\u2010lactide\u2010co\u2010glycolide) for the preparation of in\u00a0vivo detectable nanoparticles. Biomaterials 26: 4189\u20134195","journal-title":"Biomaterials"},{"key":"BFEMMM201505413_CR63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2007.05.022","volume":"122","author":"G Tosi","year":"2007","unstructured":"Tosi G, Costantino L, Rivasi F, Ruozi B, Leo E, Vergoni AV, Tacchi R, Bertolini A, Vandelli MA, Forni F (2007) Targeting the central nervous system: in\u00a0vivo experiments with peptide\u2010derivatized nanoparticles loaded with Loperamide and Rhodamine\u2010123. J Control Release 122: 1\u20139","journal-title":"J Control Release"},{"key":"BFEMMM201505413_CR64","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1517\/17425247.5.2.155","volume":"5","author":"G Tosi","year":"2008","unstructured":"Tosi G, Costantino L, Ruozi B, Forni F, Vandelli MA (2008) Polymeric nanoparticles for the drug delivery to the central nervous system. Expert Opin Drug Deliv 5: 155\u2013174","journal-title":"Expert Opin Drug Deliv"},{"key":"BFEMMM201505413_CR65","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jconrel.2010.03.008","volume":"145","author":"G Tosi","year":"2010","unstructured":"Tosi G, Vergoni AV, Ruozi B, Bondioli L, Badiali L, Rivasi F, Costantino L, Forni F, Vandelli MA (2010) Sialic acid and glycopeptides conjugated PLGA nanoparticles for central nervous system targeting: in\u00a0vivo pharmacological evidence and biodistribution. J Control Release 145: 49\u201357","journal-title":"J Control Release"},{"key":"BFEMMM201505413_CR66","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s00702-010-0497-1","volume":"118","author":"G Tosi","year":"2011","unstructured":"Tosi G, Bondioli L, Ruozi B, Badiali L, Severini GM, Biffi S, De Vita A, Bortot B, Dolcetta D, Forni F et\u00a0al (2011a) NIR\u2010labeled nanoparticles engineered for brain targeting: in\u00a0vivo optical imaging application and fluorescent microscopy evidences. J Neural Transm 118: 145\u2013153","journal-title":"J Neural Transm"},{"key":"BFEMMM201505413_CR67","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2217\/nnm.11.11","volume":"6","author":"G Tosi","year":"2011","unstructured":"Tosi G, Fano RA, Bondioli L, Badiali L, Benassi R, Rivasi F, Ruozi B, Forni F, Vandelli MA (2011b) Investigation on mechanisms of glycopeptide nanoparticles for drug delivery across the blood\u2010brain barrier. Nanomedicine 6: 423\u2013436","journal-title":"Nanomedicine"},{"key":"BFEMMM201505413_CR68","doi-asserted-by":"crossref","first-page":"365","DOI":"10.2217\/nnm.11.98","volume":"7","author":"G Tosi","year":"2012","unstructured":"Tosi G, Badiali L, Ruozi B, Vergoni AV, Bondioli L, Ferrari A, Rivasi F, Forni F, Vandelli MA (2012) Can leptin\u2010derived sequence\u2010modified nanoparticles be suitable tools for brain delivery? Nanomedicine 7: 365\u2013382","journal-title":"Nanomedicine"},{"key":"BFEMMM201505413_CR69","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jconrel.2014.01.004","volume":"177","author":"G Tosi","year":"2014","unstructured":"Tosi G, Vilella A, Chhabra R, Schmeisser MJ, Boeckers TM, Ruozi B, Vandelli MA, Forni F, Zoli M, Grabrucker AM (2014) Insight on the fate of CNS\u2010targeted nanoparticles. Part II: intercellular neuronal cell\u2010to\u2010cell transport. J Control Release 177: 96\u2013107","journal-title":"J Control Release"},{"key":"BFEMMM201505413_CR70","first-page":"388","volume":"73C","author":"U Trager","year":"2014","unstructured":"Trager U, Andre R, Magnusson\u2010Lind A, Miller JR, Connolly C, Weiss A, Grueninger S, Silajdzic E, Smith DL, Leavitt BR et\u00a0al (2014) Characterisation of immune cell function in fragment and full\u2010length Huntington's disease mouse models. Neurobiol Dis 73C: 388\u2013398","journal-title":"Neurobiol Dis"},{"key":"BFEMMM201505413_CR71","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1093\/hmg\/ddl434","volume":"15","author":"E Trushina","year":"2006","unstructured":"Trushina E, Singh RD, Dyer RB, Cao S, Shah VH, Parton RG, Pagano RE, McMurray CT (2006) Mutant huntingtin inhibits clathrin\u2010independent endocytosis and causes accumulation of cholesterol in\u00a0vitro and in\u00a0vivo. Hum Mol Genet 15: 3578\u20133591","journal-title":"Hum Mol Genet"},{"key":"BFEMMM201505413_CR72","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/hmg\/ddt406","volume":"23","author":"E Trushina","year":"2014","unstructured":"Trushina E, Canaria CA, Lee DY, McMurray CT (2014) Loss of caveolin\u20101 expression in knock\u2010in mouse model of Huntington's disease suppresses pathophysiology in\u00a0vivo. Hum Mol Genet 23: 129\u2013144","journal-title":"Hum Mol Genet"},{"key":"BFEMMM201505413_CR73","doi-asserted-by":"crossref","first-page":"9932","DOI":"10.1523\/JNEUROSCI.3355-05.2005","volume":"25","author":"M Valenza","year":"2005","unstructured":"Valenza M, Rigamonti D, Goffredo D, Zuccato C, Fenu S, Jamot L, Strand A, Tarditi A, Woodman B, Racchi M et\u00a0al (2005) Dysfunction of the cholesterol biosynthetic pathway in Huntington's disease. J Neurosci 25: 9932\u20139939","journal-title":"J Neurosci"},{"key":"BFEMMM201505413_CR74","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.pneurobio.2006.09.005","volume":"80","author":"M Valenza","year":"2006","unstructured":"Valenza M, Cattaneo E (2006) Cholesterol dysfunction in neurodegenerative diseases: is Huntington's disease in the list? Prog Neurobiol 80: 165\u2013176","journal-title":"Prog Neurobiol"},{"key":"BFEMMM201505413_CR75","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1093\/hmg\/ddm170","volume":"16","author":"M Valenza","year":"2007","unstructured":"Valenza M, Carroll JB, Leoni V, Bertram LN, Bjorkhem I, Singaraja RR, Di Donato S, Lutjohann D, Hayden MR, Cattaneo E (2007a) Cholesterol biosynthesis pathway is disturbed in YAC128 mice and is modulated by huntingtin mutation. Hum Mol Genet 16: 2187\u20132198","journal-title":"Hum Mol Genet"},{"key":"BFEMMM201505413_CR76","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.nbd.2007.07.004","volume":"28","author":"M Valenza","year":"2007","unstructured":"Valenza M, Leoni V, Tarditi A, Mariotti C, Bjorkhem I, Di Donato S, Cattaneo E (2007b) Progressive dysfunction of the cholesterol biosynthesis pathway in the R6\/2 mouse model of Huntington's disease. Neurobiol Dis 28: 133\u2013142","journal-title":"Neurobiol Dis"},{"key":"BFEMMM201505413_CR77","doi-asserted-by":"crossref","first-page":"10844","DOI":"10.1523\/JNEUROSCI.0917-10.2010","volume":"30","author":"M Valenza","year":"2010","unstructured":"Valenza M, Leoni V, Karasinska JM, Petricca L, Fan J, Carroll J, Pouladi MA, Fossale E, Nguyen HP, Riess O et\u00a0al (2010) Cholesterol defect is marked across multiple rodent models of Huntington's disease and is manifest in astrocytes. J Neurosci 30: 10844\u201310850","journal-title":"J Neurosci"},{"key":"BFEMMM201505413_CR78","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/cdd.2014.162","volume":"22","author":"M Valenza","year":"2015","unstructured":"Valenza M, Marullo M, Di Paolo E, Cesana E, Zuccato C, Biella G, Cattaneo E (2015) Disruption of astrocyte\u2010neuron cholesterol cross talk affects neuronal function in Huntington's disease. Cell Death Differ 22: 690\u2013702","journal-title":"Cell Death Differ"},{"key":"BFEMMM201505413_CR79","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.nano.2009.02.005","volume":"5","author":"AV Vergoni","year":"2009","unstructured":"Vergoni AV, Tosi G, Tacchi R, Vandelli MA, Bertolini A, Costantino L (2009) Nanoparticles as drug delivery agents specific for CNS: in\u00a0vivo biodistribution. Nanomedicine 5: 369\u2013377","journal-title":"Nanomedicine"},{"key":"BFEMMM201505413_CR80","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jconrel.2013.11.023","volume":"174","author":"A Vilella","year":"2014","unstructured":"Vilella A, Tosi G, Grabrucker AM, Ruozi B, Belletti D, Vandelli MA, Boeckers TM, Forni F, Zoli M (2014) Insight on the fate of CNS\u2010targeted nanoparticles. Part I: Rab5\u2010dependent cell\u2010specific uptake and distribution. J Control Release 174: 195\u2013201","journal-title":"J Control Release"},{"key":"BFEMMM201505413_CR81","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1056\/NEJMoa1304369","volume":"369","author":"DD Von Hoff","year":"2013","unstructured":"Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN et\u00a0al (2013) Increased survival in pancreatic cancer with nab\u2010paclitaxel plus gemcitabine. N Engl J Med 369: 1691\u20131703","journal-title":"N Engl J Med"},{"key":"BFEMMM201505413_CR82","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1097\/00005072-199805000-00001","volume":"57","author":"JP Vonsattel","year":"1998","unstructured":"Vonsattel JP, DiFiglia M (1998) Huntington disease. J Neuropathol Exp Neurol 57: 369\u2013384","journal-title":"J Neuropathol Exp Neurol"},{"key":"BFEMMM201505413_CR83","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1152\/physrev.00041.2009","volume":"90","author":"C Zuccato","year":"2010","unstructured":"Zuccato C, Valenza M, Cattaneo E (2010) Molecular mechanisms and potential therapeutical targets in Huntington's disease. Physiol Rev 90: 905\u2013981","journal-title":"Physiol Rev"},{"key":"BFEMMM201505413_CR84","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/978-3-642-45106-5_14","volume":"220","author":"C Zuccato","year":"2014","unstructured":"Zuccato C, Cattaneo E (2014) Huntington's disease. Handb Exp Pharmacol 220: 357\u2013409","journal-title":"Handb Exp Pharmacol"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.201505413.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/emmm.201505413","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/emmm.201505413\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/emmm.201505413","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.201505413.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:16:23Z","timestamp":1779084983000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/emmm.201505413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,20]]},"references-count":85,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,12,1]]}},"alternative-id":["BFEMMM201505413"],"URL":"https:\/\/doi.org\/10.15252\/emmm.201505413","relation":{},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,20]]},"assertion":[{"value":"6 May 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2015","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2015","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2015","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}