{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T14:43:15Z","timestamp":1794580995003,"version":"4.9.1"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS118066"],"award-info":[{"award-number":["R01NS118066"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS096282"],"award-info":[{"award-number":["R01 NS096282"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["Intramural Research Program"],"award-info":[{"award-number":["Intramural Research Program"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hereditary spastic paraplegias (HSPs) are caused by a length-dependent axonopathy of long corticospinal neurons, but how axons of these cortical projection neurons (PNs) degenerate remains elusive. We generated isogenic human pluripotent stem cell (hPSC) lines for two<jats:italic>ATL1<\/jats:italic>missense mutations associated with SPG3A, the most common early-onset autosomal dominant HSP. In hPSC-derived cortical PNs,<jats:italic>ATL1<\/jats:italic>mutations resulted in reduced axonal outgrowth, impaired axonal transport, and accumulated axonal swellings, recapitulating disease-specific phenotypes. Importantly,<jats:italic>ATL1<\/jats:italic>mutations dysregulated proteolipid gene expression, reduced lipid droplet size in astrocytes, and unexpectedly disrupted cholesterol transfer from glia to neurons, leading to cholesterol deficiency in SPG3A cortical PNs. Applying cholesterol or conditioned medium from control astrocytes, a major source of cholesterol in the brain, rescued aberrant axonal transport and swellings in SPG3A cortical PNs. Furthermore, treatment with the NR1H2 agonist GW3965 corrected lipid droplet defects in SPG3A astrocytes and promoted cholesterol efflux from astrocytes, leading to restoration of cholesterol levels and rescue of axonal degeneration in SPG3A cortical PNs. These results reveal a non-cell autonomous mechanism underlying axonal degeneration of cortical PNs mediated by impaired cholesterol homeostasis in glia.<\/jats:p>","DOI":"10.1186\/s40478-020-01088-0","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T10:05:56Z","timestamp":1607335556000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Impaired lipid metabolism in astrocytes underlies degeneration of cortical projection neurons in hereditary spastic paraplegia"],"prefix":"10.1186","volume":"8","author":[{"given":"Yongchao","family":"Mou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle R.","family":"Denton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael O.","family":"Duff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Blackstone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Chun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1899-9134","authenticated-orcid":false,"given":"Xue-Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"1088_CR1","doi-asserted-by":"publisher","first-page":"12799","DOI":"10.1074\/jbc.M601019200","volume":"281","author":"K Abildayeva","year":"2006","unstructured":"Abildayeva K, Jansen PJ, Hirsch-Reinshagen V, Bloks VW, Bakker AH, Ramaekers FC, de Vente J, Groen AK, Wellington CL, Kuipers F et al (2006) 24(S)-hydroxycholesterol participates in a liver X receptor-controlled pathway in astrocytes that regulates apolipoprotein E-mediated cholesterol efflux. J Biol Chem 281:12799\u201312808. https:\/\/doi.org\/10.1074\/jbc.M601019200","journal-title":"J Biol Chem"},{"key":"1088_CR2","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.conb.2018.04.025","volume":"51","author":"C Blackstone","year":"2018","unstructured":"Blackstone C (2018) Converging cellular themes for the hereditary spastic paraplegias. Curr Opin Neurobiol 51:139\u2013146. https:\/\/doi.org\/10.1016\/j.conb.2018.04.025","journal-title":"Curr Opin Neurobiol"},{"key":"1088_CR3","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/nrn2946","volume":"12","author":"C Blackstone","year":"2010","unstructured":"Blackstone C, O\u2019Kane CJ, Reid E (2010) Hereditary spastic paraplegias: membrane traffic and the motor pathway. Nat Rev Neurosci 12:31\u201342. https:\/\/doi.org\/10.1038\/nrn2946","journal-title":"Nat Rev Neurosci"},{"key":"1088_CR4","doi-asserted-by":"publisher","DOI":"10.3791\/50321","author":"EM Boisvert","year":"2013","unstructured":"Boisvert EM, Denton K, Lei L, Li XJ (2013) The specification of telencephalic glutamatergic neurons from human pluripotent stem cells. J Vis Exp. https:\/\/doi.org\/10.3791\/50321","journal-title":"J Vis Exp"},{"key":"1088_CR5","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1002\/stem.408","volume":"28","author":"L Borghese","year":"2010","unstructured":"Borghese L, Dolezalova D, Opitz T, Haupt S, Leinhaas A, Steinfarz B, Koch P, Edenhofer F, Hampl A, Brustle O (2010) Inhibition of notch signaling in human embryonic stem cell-derived neural stem cells delays G1\/S phase transition and accelerates neuronal differentiation in vitro and in vivo. Stem Cells 28:955\u2013964. https:\/\/doi.org\/10.1002\/stem.408","journal-title":"Stem Cells"},{"key":"1088_CR6","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/s42003-019-0615-z615","volume":"2","author":"M Boutry","year":"2019","unstructured":"Boutry M, Pierga A, Matusiak R, Branchu J, Houllegatte M, Ibrahim Y, Balse E, El Hachimi KH, Brice A, Stevanin G et al (2019) Loss of spatacsin impairs cholesterol trafficking and calcium homeostasis. Commun Biol 2:380. https:\/\/doi.org\/10.1038\/s42003-019-0615-z615","journal-title":"Commun Biol"},{"key":"1088_CR7","doi-asserted-by":"publisher","first-page":"11896","DOI":"10.1523\/JNEUROSCI.1898-10.2010","volume":"30","author":"G Cermenati","year":"2010","unstructured":"Cermenati G, Giatti S, Cavaletti G, Bianchi R, Maschi O, Pesaresi M, Abbiati F, Volonterio A, Saez E, Caruso D et al (2010) Activation of the liver X receptor increases neuroactive steroid levels and protects from diabetes-induced peripheral neuropathy. J Neurosci Off J Soc Neurosc 30:11896\u201311901. https:\/\/doi.org\/10.1523\/JNEUROSCI.1898-10.2010","journal-title":"J Neurosci Off J Soc Neurosc"},{"key":"1088_CR8","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.bbalip.2012.09.007","volume":"1831","author":"J Chen","year":"2013","unstructured":"Chen J, Zhang X, Kusumo H, Costa LG, Guizzetti M (2013) Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis. Biochim Biophys Acta 1831:263\u2013275. https:\/\/doi.org\/10.1016\/j.bbalip.2012.09.007","journal-title":"Biochim Biophys Acta"},{"key":"1088_CR9","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1016\/j.jpain.2013.03.005","volume":"14","author":"HT Cheng","year":"2013","unstructured":"Cheng HT, Dauch JR, Porzio MT, Yanik BM, Hsieh W, Smith AG, Singleton JR, Feldman EL (2013) Increased axonal regeneration and swellings in intraepidermal nerve fibers characterize painful phenotypes of diabetic neuropathy. J Pain 14:941\u2013947. https:\/\/doi.org\/10.1016\/j.jpain.2013.03.005","journal-title":"J Pain"},{"key":"1088_CR10","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.envres.2017.07.048","volume":"159","author":"CE Cicero","year":"2017","unstructured":"Cicero CE, Mostile G, Vasta R, Rapisarda V, Signorelli SS, Ferrante M, Zappia M, Nicoletti A (2017) Metals and neurodegenerative diseases. A systematic review. Environ Res 159:82\u201394. https:\/\/doi.org\/10.1016\/j.envres.2017.07.048","journal-title":"Environ Res"},{"key":"1088_CR11","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1161\/STROKEAHA.112.677682","volume":"44","author":"X Cui","year":"2013","unstructured":"Cui X, Chopp M, Zacharek A, Cui Y, Roberts C, Chen J (2013) The neurorestorative benefit of GW3965 treatment of stroke in mice. Stroke 44:153\u2013161. https:\/\/doi.org\/10.1161\/STROKEAHA.112.677682","journal-title":"Stroke"},{"key":"1088_CR12","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1002\/stem.1569","volume":"32","author":"KR Denton","year":"2014","unstructured":"Denton KR, Lei L, Grenier J, Rodionov V, Blackstone C, Li XJ (2014) Loss of spastin function results in disease-specific axonal defects in human pluripotent stem cell-based models of hereditary spastic paraplegia. Stem Cells 32:414\u2013423. https:\/\/doi.org\/10.1002\/stem.1569","journal-title":"Stem Cells"},{"key":"1088_CR13","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1515\/BC.2009.035","volume":"390","author":"JM Dietschy","year":"2009","unstructured":"Dietschy JM (2009) Central nervous system: cholesterol turnover, brain development and neurodegeneration. Biol Chem 390:287\u2013293. https:\/\/doi.org\/10.1515\/BC.2009.035","journal-title":"Biol Chem"},{"key":"1088_CR14","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1083\/jcb.200808041","volume":"184","author":"SW Eastman","year":"2009","unstructured":"Eastman SW, Yassaee M, Bieniasz PD (2009) A role for ubiquitin ligases and Spartin\/SPG20 in lipid droplet turnover. J Cell Biol 184:881\u2013894. https:\/\/doi.org\/10.1083\/jcb.200808041","journal-title":"J Cell Biol"},{"key":"1088_CR15","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1002\/humu.22521","volume":"35","author":"J Falk","year":"2014","unstructured":"Falk J, Rohde M, Bekhite MM, Neugebauer S, Hemmerich P, Kiehntopf M, Deufel T, Hubner CA, Beetz C (2014) Functional mutation analysis provides evidence for a role of REEP1 in lipid droplet biology. Hum Mutat 35:497\u2013504. https:\/\/doi.org\/10.1002\/humu.22521","journal-title":"Hum Mutat"},{"key":"1088_CR16","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1046\/j.0022-3042.2001.00686.x","volume":"80","author":"QW Fan","year":"2002","unstructured":"Fan QW, Yu W, Gong JS, Zou K, Sawamura N, Senda T, Yanagisawa K, Michikawa M (2002) Cholesterol-dependent modulation of dendrite outgrowth and microtubule stability in cultured neurons. J Neurochem 80:178\u2013190","journal-title":"J Neurochem"},{"key":"1088_CR17","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1038\/nn.2662","volume":"13","author":"C Fassier","year":"2010","unstructured":"Fassier C, Hutt JA, Scholpp S, Lumsden A, Giros B, Nothias F, Schneider-Maunoury S, Houart C, Hazan J (2010) Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway. Nat Neurosci 13:1380\u20131387. https:\/\/doi.org\/10.1038\/nn.2662","journal-title":"Nat Neurosci"},{"key":"1088_CR18","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1242\/dmm.008946","volume":"6","author":"C Fassier","year":"2013","unstructured":"Fassier C, Tarrade A, Peris L, Courageot S, Mailly P, Dalard C, Delga S, Roblot N, Lefevre J, Job D et al (2013) Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice. Dis Model Mech 6:72\u201383. https:\/\/doi.org\/10.1242\/dmm.008946","journal-title":"Dis Model Mech"},{"key":"1088_CR19","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.tem.2011.02.004","volume":"22","author":"W Fei","year":"2011","unstructured":"Fei W, Du X, Yang H (2011) Seipin, adipogenesis and lipid droplets. Trends Endocrinol Metab 22:204\u2013210. https:\/\/doi.org\/10.1016\/j.tem.2011.02.004","journal-title":"Trends Endocrinol Metab"},{"key":"1088_CR20","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1172\/JCI20138","volume":"113","author":"F Ferreirinha","year":"2004","unstructured":"Ferreirinha F, Quattrini A, Pirozzi M, Valsecchi V, Dina G, Broccoli V, Auricchio A, Piemonte F, Tozzi G, Gaeta L et al (2004) Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport. J Clin Invest 113:231\u2013242. https:\/\/doi.org\/10.1172\/JCI20138","journal-title":"J Clin Invest"},{"key":"1088_CR21","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1073\/pnas.1620506114","volume":"114","author":"HA Ferris","year":"2017","unstructured":"Ferris HA, Perry RJ, Moreira GV, Shulman GI, Horton JD, Kahn CR (2017) Loss of astrocyte cholesterol synthesis disrupts neuronal function and alters whole-body metabolism. Proc Natl Acad Sci U S A 114:1189\u20131194. https:\/\/doi.org\/10.1073\/pnas.1620506114","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1088_CR22","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s11910-996-0011-1","volume":"6","author":"JK Fink","year":"2006","unstructured":"Fink JK (2006) Hereditary spastic paraplegia. Curr Neurol Neurosci Rep 6:65\u201376. https:\/\/doi.org\/10.1007\/s11910-996-0011-1","journal-title":"Curr Neurol Neurosci Rep"},{"key":"1088_CR23","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1159\/000107704","volume":"4","author":"LR Fischer","year":"2007","unstructured":"Fischer LR, Glass JD (2007) Axonal degeneration in motor neuron disease. Neurodegener Dis 4:431\u2013442. https:\/\/doi.org\/10.1159\/000107704","journal-title":"Neurodegener Dis"},{"key":"1088_CR24","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.cmet.2012.03.007","volume":"15","author":"S Fu","year":"2012","unstructured":"Fu S, Watkins SM, Hotamisligil GS (2012) The role of endoplasmic reticulum in hepatic lipid homeostasis and stress signaling. Cell Metab 15:623\u2013634. https:\/\/doi.org\/10.1016\/j.cmet.2012.03.007","journal-title":"Cell Metab"},{"key":"1088_CR25","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1523\/JNEUROSCI.21-03-00812.2001","volume":"21","author":"S Grehan","year":"2001","unstructured":"Grehan S, Tse E, Taylor JM (2001) Two distal downstream enhancers direct expression of the human apolipoprotein E gene to astrocytes in the brain. J Neurosci 21:812\u2013822","journal-title":"J Neurosci"},{"key":"1088_CR26","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlw114","author":"V Gudi","year":"2017","unstructured":"Gudi V, Gai L, Herder V, Tejedor LS, Kipp M, Amor S, Suhs KW, Hansmann F, Beineke A, Baumgartner W et al (2017) Synaptophysin is a reliable marker for axonal damage. J Neuropathol Exp Neurol. https:\/\/doi.org\/10.1093\/jnen\/nlw114","journal-title":"J Neuropathol Exp Neurol"},{"key":"1088_CR27","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.cell.2009.05.025","volume":"138","author":"J Hu","year":"2009","unstructured":"Hu J, Shibata Y, Zhu PP, Voss C, Rismanchi N, Prinz WA, Rapoport TA, Blackstone C (2009) A class of dynamin-like GTPases involved in the generation of the tubular ER network. Cell 138:549\u2013561. https:\/\/doi.org\/10.1016\/j.cell.2009.05.025","journal-title":"Cell"},{"key":"1088_CR28","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.expneurol.2012.06.003","volume":"246","author":"NM Kanaan","year":"2013","unstructured":"Kanaan NM, Pigino GF, Brady ST, Lazarov O, Binder LI, Morfini GA (2013) Axonal degeneration in Alzheimer\u2019s disease: when signaling abnormalities meet the axonal transport system. Exp Neurol 246:44\u201353. https:\/\/doi.org\/10.1016\/j.expneurol.2012.06.003","journal-title":"Exp Neurol"},{"key":"1088_CR29","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1111\/j.1471-4159.2009.06104.x","volume":"110","author":"PR Kasher","year":"2009","unstructured":"Kasher PR, De Vos KJ, Wharton SB, Manser C, Bennett EJ, Bingley M, Wood JD, Milner R, McDermott CJ, Miller CC et al (2009) Direct evidence for axonal transport defects in a novel mouse model of mutant spastin-induced hereditary spastic paraplegia (HSP) and human HSP patients. J Neurochem 110:34\u201344. https:\/\/doi.org\/10.1111\/j.1471-4159.2009.06104.x","journal-title":"J Neurochem"},{"key":"1088_CR30","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1016\/j.celrep.2013.04.015","volume":"3","author":"RW Klemm","year":"2013","unstructured":"Klemm RW, Norton JP, Cole RA, Li CS, Park SH, Crane MM, Li L, Jin D, Boye-Doe A, Liu TY et al (2013) A conserved role for atlastin GTPases in regulating lipid droplet size. Cell Rep 3:1465\u20131475. https:\/\/doi.org\/10.1016\/j.celrep.2013.04.015","journal-title":"Cell Rep"},{"key":"1088_CR31","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1038\/nprot.2011.405","volume":"6","author":"R Krencik","year":"2011","unstructured":"Krencik R, Zhang SC (2011) Directed differentiation of functional astroglial subtypes from human pluripotent stem cells. Nat Protoc 6:1710\u20131717. https:\/\/doi.org\/10.1038\/nprot.2011.405","journal-title":"Nat Protoc"},{"key":"1088_CR32","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1212\/01.wnl.0000070781.92512.a4","volume":"61","author":"G Lauria","year":"2003","unstructured":"Lauria G, Morbin M, Lombardi R, Borgna M, Mazzoleni G, Sghirlanzoni A, Pareyson D (2003) Axonal swellings predict the degeneration of epidermal nerve fibers in painful neuropathies. Neurology 61:631\u2013636. https:\/\/doi.org\/10.1212\/01.wnl.0000070781.92512.a4","journal-title":"Neurology"},{"key":"1088_CR33","doi-asserted-by":"publisher","first-page":"3590","DOI":"10.1096\/fj.201800779RR","volume":"33","author":"M Lee","year":"2019","unstructured":"Lee M, Moon Y, Lee S, Lee C, Jun Y (2019) Ergosterol interacts with Sey1p to promote atlastin-mediated endoplasmic reticulum membrane fusion in Saccharomyces cerevisiae. FASEB J 33:3590\u20133600. https:\/\/doi.org\/10.1096\/fj.201800779RR","journal-title":"FASEB J"},{"key":"1088_CR34","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.ydbio.2009.03.019","volume":"330","author":"M Lee","year":"2009","unstructured":"Lee M, Paik SK, Lee MJ, Kim YJ, Kim S, Nahm M, Oh SJ, Kim HM, Yim J, Lee CJ et al (2009) Drosophila Atlastin regulates the stability of muscle microtubules and is required for synapse development. Dev Biol 330:250\u2013262. https:\/\/doi.org\/10.1016\/j.ydbio.2009.03.019","journal-title":"Dev Biol"},{"key":"1088_CR35","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/nbt1063","volume":"23","author":"XJ Li","year":"2005","unstructured":"Li XJ, Du ZW, Zarnowska ED, Pankratz M, Hansen LO, Pearce RA, Zhang SC (2005) Specification of motoneurons from human embryonic stem cells. Nat Biotechnol 23:215\u2013221. https:\/\/doi.org\/10.1038\/nbt1063","journal-title":"Nat Biotechnol"},{"key":"1088_CR36","doi-asserted-by":"publisher","first-page":"4055","DOI":"10.1242\/dev.036624","volume":"136","author":"XJ Li","year":"2009","unstructured":"Li XJ, Zhang X, Johnson MA, Wang ZB, Lavaute T, Zhang SC (2009) Coordination of sonic hedgehog and Wnt signaling determines ventral and dorsal telencephalic neuron types from human embryonic stem cells. Development 136:4055\u20134063. https:\/\/doi.org\/10.1242\/dev.036624","journal-title":"Development"},{"key":"1088_CR37","doi-asserted-by":"publisher","first-page":"24231","DOI":"10.1074\/jbc.M116.759795","volume":"291","author":"AE Libby","year":"2016","unstructured":"Libby AE, Bales E, Orlicky DJ, McManaman JL (2016) Perilipin-2 deletion impairs hepatic lipid accumulation by interfering with sterol regulatory element-binding protein (SREBP) activation and altering the hepatic lipidome. J Biol Chem 291:24231\u201324246. https:\/\/doi.org\/10.1074\/jbc.M116.759795","journal-title":"J Biol Chem"},{"key":"1088_CR38","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/s41467-019-08478-6","volume":"10","author":"X Liu","year":"2019","unstructured":"Liu X, Guo X, Niu L, Li X, Sun F, Hu J, Wang X, Shen K (2019) Atlastin-1 regulates morphology and function of endoplasmic reticulum in dendrites. Nat Commun 10:568. https:\/\/doi.org\/10.1038\/s41467-019-08478-6","journal-title":"Nat Commun"},{"key":"1088_CR39","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.neuron.2014.10.019","volume":"84","author":"S Maday","year":"2014","unstructured":"Maday S, Twelvetrees AE, Moughamian AJ, Holzbaur EL (2014) Axonal transport: cargo-specific mechanisms of motility and regulation. Neuron 84:292\u2013309. https:\/\/doi.org\/10.1016\/j.neuron.2014.10.019","journal-title":"Neuron"},{"key":"1088_CR40","first-page":"A215","volume":"13","author":"MH Marra","year":"2015","unstructured":"Marra MH, Tobias ZJ, Cohen HR, Glover G, Weissman TA (2015) In vivo time-lapse imaging in the zebrafish lateral line: a flexible, open-ended research project for an undergraduate neurobiology laboratory course. J Undergrad Neurosci Educ 13:A215\u2013224","journal-title":"J Undergrad Neurosci Educ"},{"key":"1088_CR41","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, Pfrieger FW (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":"1088_CR42","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s40478-015-0240-0","volume":"3","author":"KE McAleese","year":"2015","unstructured":"McAleese KE, Firbank M, Dey M, Colloby SJ, Walker L, Johnson M, Beverley JR, Taylor JP, Thomas AJ, O\u2019Brien JT et al (2015) Cortical tau load is associated with white matter hyperintensities. Acta Neuropathol Commun 3:60. https:\/\/doi.org\/10.1186\/s40478-015-0240-0","journal-title":"Acta Neuropathol Commun"},{"key":"1088_CR43","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1007\/s00401-017-1738-2","volume":"134","author":"KE McAleese","year":"2017","unstructured":"McAleese KE, Walker L, Graham S, Moya ELJ, Johnson M, Erskine D, Colloby SJ, Dey M, Martin-Ruiz C, Taylor JP et al (2017) Parietal white matter lesions in Alzheimer\u2019s disease are associated with cortical neurodegenerative pathology, but not with small vessel disease. Acta Neuropathol 134:459\u2013473. https:\/\/doi.org\/10.1007\/s00401-017-1738-2","journal-title":"Acta Neuropathol"},{"key":"1088_CR44","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1111\/j.1399-0004.2010.01501.xcge1501","volume":"79","author":"DS McCorquodale 3rd","year":"2011","unstructured":"McCorquodale DS 3rd, Ozomaro U, Huang J, Montenegro G, Kushman A, Citrigno L, Price J, Speziani F, Pericak-Vance MA, Zuchner S (2011) Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia. Clin Genet 79:523\u2013530. https:\/\/doi.org\/10.1111\/j.1399-0004.2010.01501.xcge1501","journal-title":"Clin Genet"},{"key":"1088_CR45","doi-asserted-by":"publisher","DOI":"10.3791\/60548","author":"Y Mou","year":"2020","unstructured":"Mou Y, Mukte S, Chai E, Dein J, Li XJ (2020) Analyzing mitochondrial transport and morphology in human induced pluripotent stem cell-derived neurons in hereditary spastic paraplegia. J Vis Exp. https:\/\/doi.org\/10.3791\/60548","journal-title":"J Vis Exp"},{"key":"1088_CR46","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1111\/j.1471-4159.2009.06258.x","volume":"110","author":"MP Muriel","year":"2009","unstructured":"Muriel MP, Dauphin A, Namekawa M, Gervais A, Brice A, Ruberg M (2009) Atlastin-1, the dynamin-like GTPase responsible for spastic paraplegia SPG3A, remodels lipid membranes and may form tubules and vesicles in the endoplasmic reticulum. J Neurochem 110:1607\u20131616. https:\/\/doi.org\/10.1111\/j.1471-4159.2009.06258.x","journal-title":"J Neurochem"},{"key":"1088_CR47","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1212\/01.wnl.0000191390.20564.8e","volume":"66","author":"M Namekawa","year":"2006","unstructured":"Namekawa M, Ribai P, Nelson I, Forlani S, Fellmann F, Goizet C, Depienne C, Stevanin G, Ruberg M, Durr A et al (2006) SPG3A is the most frequent cause of hereditary spastic paraplegia with onset before age 10 years. Neurology 66:112\u2013114. https:\/\/doi.org\/10.1212\/01.wnl.0000191390.20564.8e","journal-title":"Neurology"},{"key":"1088_CR48","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1111\/j.1471-4159.2009.05917.x","volume":"109","author":"K Nieweg","year":"2009","unstructured":"Nieweg K, Schaller H, Pfrieger FW (2009) Marked differences in cholesterol synthesis between neurons and glial cells from postnatal rats. J Neurochem 109:125\u2013134. https:\/\/doi.org\/10.1111\/j.1471-4159.2009.05917.x","journal-title":"J Neurochem"},{"key":"1088_CR49","doi-asserted-by":"publisher","first-page":"14029","DOI":"10.1073\/pnas.1908409116","volume":"116","author":"L Niu","year":"2019","unstructured":"Niu L, Ma T, Yang F, Yan B, Tang X, Yin H, Wu Q, Huang Y, Yao ZP, Wang J et al (2019) Atlastin-mediated membrane tethering is critical for cargo mobility and exit from the endoplasmic reticulum. Proc Natl Acad Sci U S A 116:14029\u201314038. https:\/\/doi.org\/10.1073\/pnas.1908409116","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1088_CR50","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1038\/nature08280","volume":"460","author":"G Orso","year":"2009","unstructured":"Orso G, Pendin D, Liu S, Tosetto J, Moss TJ, Faust JE, Micaroni M, Egorova A, Martinuzzi A, McNew JA et al (2009) Homotypic fusion of ER membranes requires the dynamin-like GTPase atlastin. Nature 460:978\u2013983. https:\/\/doi.org\/10.1038\/nature08280","journal-title":"Nature"},{"key":"1088_CR51","doi-asserted-by":"publisher","first-page":"e1005149","DOI":"10.1371\/journal.pgen.1005149","volume":"11","author":"C Papadopoulos","year":"2015","unstructured":"Papadopoulos C, Orso G, Mancuso G, Herholz M, Gumeni S, Tadepalle N, Jungst C, Tzschichholz A, Schauss A, Honing S et al (2015) Spastin binds to lipid droplets and affects lipid metabolism. PLoS Genet 11:e1005149. https:\/\/doi.org\/10.1371\/journal.pgen.1005149","journal-title":"PLoS Genet"},{"key":"1088_CR52","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1172\/jci40979\/40979","volume":"120","author":"SH Park","year":"2010","unstructured":"Park SH, Zhu PP, Parker RL, Blackstone C (2010) Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network. J Clin Invest 120:1097\u20131110. https:\/\/doi.org\/10.1172\/jci40979\/40979","journal-title":"J Clin Invest"},{"key":"1088_CR53","doi-asserted-by":"publisher","first-page":"e28202","DOI":"10.7554\/elife.28202","volume":"6","author":"S Pawar","year":"2017","unstructured":"Pawar S, Ungricht R, Tiefenboeck P, Leroux JC, Kutay U (2017) Efficient protein targeting to the inner nuclear membrane requires Atlastin-dependent maintenance of ER topology. Elife 6:e28202. https:\/\/doi.org\/10.7554\/elife.28202","journal-title":"Elife"},{"key":"1088_CR54","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41431-019-0497-z","volume":"28","author":"M Pennings","year":"2020","unstructured":"Pennings M, Schouten MI, van Gaalen J, Meijer RPP, de Bot ST, Kriek M, Saris CGJ, van den Berg LH, van Es MA, Zuidgeest DMH et al (2020) KIF1A variants are a frequent cause of autosomal dominant hereditary spastic paraplegia. Eur J Hum Genet 28:40\u201349. https:\/\/doi.org\/10.1038\/s41431-019-0497-z","journal-title":"Eur J Hum Genet"},{"key":"1088_CR55","doi-asserted-by":"publisher","first-page":"4859","DOI":"10.1093\/hmg\/ddu200","volume":"23","author":"F Perez-Branguli","year":"2014","unstructured":"Perez-Branguli F, Mishra HK, Prots I, Havlicek S, Kohl Z, Saul D, Rummel C, Dorca-Arevalo J, Regensburger M, Graef D et al (2014) Dysfunction of spatacsin leads to axonal pathology in SPG11-linked hereditary spastic paraplegia. Hum Mol Genet 23:4859\u20134874. https:\/\/doi.org\/10.1093\/hmg\/ddu200","journal-title":"Hum Mol Genet"},{"key":"1088_CR56","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1007\/s00018-003-3018-7","volume":"60","author":"FW Pfrieger","year":"2003","unstructured":"Pfrieger FW (2003) Cholesterol homeostasis and function in neurons of the central nervous system. Cell Mol Life Sci 60:1158\u20131171. https:\/\/doi.org\/10.1007\/s00018-003-3018-7","journal-title":"Cell Mol Life Sci"},{"key":"1088_CR57","doi-asserted-by":"publisher","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":"1088_CR58","doi-asserted-by":"crossref","first-page":"14352","DOI":"10.1016\/S0021-9258(18)47945-8","volume":"262","author":"RE Pitas","year":"1987","unstructured":"Pitas RE, Boyles JK, Lee SH, Hui D, Weisgraber KH (1987) Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B, E(LDL) receptors in the brain. J Biol Chem 262:14352\u201314360","journal-title":"J Biol Chem"},{"key":"1088_CR59","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.nbd.2017.02.009","volume":"105","author":"R Prior","year":"2017","unstructured":"Prior R, Van Helleputte L, Benoy V, Van Den Bosch L (2017) Defective axonal transport: a common pathological mechanism in inherited and acquired peripheral neuropathies. Neurobiol Dis 105:300\u2013320. https:\/\/doi.org\/10.1016\/j.nbd.2017.02.009","journal-title":"Neurobiol Dis"},{"key":"1088_CR60","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1016\/j.cell.2015.12.054","volume":"164","author":"A Rai","year":"2016","unstructured":"Rai A, Pathak D, Thakur S, Singh S, Dubey AK, Mallik R (2016) Dynein clusters into lipid microdomains on phagosomes to drive rapid transport toward lysosomes. Cell 164:722\u2013734. https:\/\/doi.org\/10.1016\/j.cell.2015.12.054","journal-title":"Cell"},{"key":"1088_CR61","doi-asserted-by":"publisher","first-page":"9615","DOI":"10.1038\/s41598-019-45246-4","volume":"9","author":"K Rehbach","year":"2019","unstructured":"Rehbach K, Kesavan J, Hauser S, Ritzenhofen S, Jungverdorben J, Schule R, Schols L, Peitz M, Brustle O (2019) Multiparametric rapid screening of neuronal process pathology for drug target identification in HSP patient-specific neurons. Sci Rep 9:9615. https:\/\/doi.org\/10.1038\/s41598-019-45246-4","journal-title":"Sci Rep"},{"key":"1088_CR62","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1136\/jmg.40.2.81","volume":"40","author":"E Reid","year":"2003","unstructured":"Reid E (2003) Science in motion: common molecular pathological themes emerge in the hereditary spastic paraplegias. J Med Genet 40:81\u201386. https:\/\/doi.org\/10.1136\/jmg.40.2.81","journal-title":"J Med Genet"},{"key":"1088_CR63","doi-asserted-by":"publisher","first-page":"104","DOI":"10.4103\/2349-3666.240602","volume":"3","author":"H Rene","year":"2016","unstructured":"Rene H, Quintanilla NK, Calabrese Barbara, Rao Mahendra, Lakshmipathy Uma (2016) BacMam-mediated gene transfer into neural cell types. Biomed Res J 3:104\u2013122. https:\/\/doi.org\/10.4103\/2349-3666.240602","journal-title":"Biomed Res J"},{"key":"1088_CR64","doi-asserted-by":"publisher","first-page":"5111","DOI":"10.1093\/hmg\/ddw315","volume":"25","author":"B Renvoise","year":"2016","unstructured":"Renvoise B, Malone B, Falgairolle M, Munasinghe J, Stadler J, Sibilla C, Park SH, Blackstone C (2016) Reep1 null mice reveal a converging role for hereditary spastic paraplegia proteins in lipid droplet regulation. Hum Mol Genet 25:5111\u20135125. https:\/\/doi.org\/10.1093\/hmg\/ddw315","journal-title":"Hum Mol Genet"},{"key":"1088_CR65","doi-asserted-by":"publisher","first-page":"3604","DOI":"10.1093\/hmg\/dds191","volume":"21","author":"B Renvoise","year":"2012","unstructured":"Renvoise B, Stadler J, Singh R, Bakowska JC, Blackstone C (2012) Spg20-\/- mice reveal multimodal functions for Troyer syndrome protein spartin in lipid droplet maintenance, cytokinesis and BMP signaling. Hum Mol Genet 21:3604\u20133618. https:\/\/doi.org\/10.1093\/hmg\/dds191","journal-title":"Hum Mol Genet"},{"key":"1088_CR66","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1038\/nn1426","volume":"8","author":"G Saher","year":"2005","unstructured":"Saher G, Brugger B, Lappe-Siefke C, Mobius W, Tozawa R, Wehr MC, Wieland F, Ishibashi S, Nave KA (2005) High cholesterol level is essential for myelin membrane growth. Nat Neurosci 8:468\u2013475. https:\/\/doi.org\/10.1038\/nn1426","journal-title":"Nat Neurosci"},{"key":"1088_CR67","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/S1474-4422(08)70258-8","volume":"7","author":"S Salinas","year":"2008","unstructured":"Salinas S, Proukakis C, Crosby A, Warner TT (2008) Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms. Lancet Neurol 7:1127\u20131138. https:\/\/doi.org\/10.1016\/S1474-4422(08)70258-8","journal-title":"Lancet Neurol"},{"key":"1088_CR68","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1038\/nrendo.2017.91","volume":"13","author":"H Shimano","year":"2017","unstructured":"Shimano H, Sato R (2017) SREBP-regulated lipid metabolism: convergent physiology\u2014divergent pathophysiology. Nat Rev Endocrinol 13:710\u2013730. https:\/\/doi.org\/10.1038\/nrendo.2017.91","journal-title":"Nat Rev Endocrinol"},{"key":"1088_CR69","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/j.1750-3639.1993.tb00729.x","volume":"3","author":"G Thiel","year":"1993","unstructured":"Thiel G (1993) Synapsin I, synapsin II, and synaptophysin: marker proteins of synaptic vesicles. Brain Pathol 3:87\u201395","journal-title":"Brain Pathol"},{"key":"1088_CR70","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nprot.2012.016","volume":"7","author":"C Trapnell","year":"2012","unstructured":"Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, Pimentel H, Salzberg SL, Rinn JL, Pachter L (2012) Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc 7:562\u2013578. https:\/\/doi.org\/10.1038\/nprot.2012.016","journal-title":"Nat Protoc"},{"key":"1088_CR71","doi-asserted-by":"publisher","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-neuron cholesterol cross talk affects neuronal function in Huntington\u2019s disease. Cell Death Differ 22:690\u2013702. https:\/\/doi.org\/10.1038\/cdd.2014.162","journal-title":"Cell Death Differ"},{"key":"1088_CR72","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/s1388-1981(00)00050-0","volume":"1486","author":"JE Vance","year":"2000","unstructured":"Vance JE, Campenot RB, Vance DE (2000) The synthesis and transport of lipids for axonal growth and nerve regeneration. Biochim Biophys Acta 1486:84\u201396. https:\/\/doi.org\/10.1016\/s1388-1981(00)00050-0","journal-title":"Biochim Biophys Acta"},{"key":"1088_CR73","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1210\/mend.16.6.0835","volume":"16","author":"KD Whitney","year":"2002","unstructured":"Whitney KD, Watson MA, Collins JL, Benson WG, Stone TM, Numerick MJ, Tippin TK, Wilson JG, Winegar DA, Kliewer SA (2002) Regulation of cholesterol homeostasis by the liver X receptors in the central nervous system. Mol Endocrinol 16:1378\u20131385. https:\/\/doi.org\/10.1210\/mend.16.6.0835","journal-title":"Mol Endocrinol"},{"key":"1088_CR74","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1007\/s13238-014-0131-3","volume":"6","author":"J Zhang","year":"2015","unstructured":"Zhang J, Liu Q (2015) Cholesterol metabolism and homeostasis in the brain. Protein Cell 6:254\u2013264. https:\/\/doi.org\/10.1007\/s13238-014-0131-3","journal-title":"Protein Cell"},{"key":"1088_CR75","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.yexcr.2016.09.015","volume":"349","author":"G Zhao","year":"2016","unstructured":"Zhao G, Zhu PP, Renvoise B, Maldonado-Baez L, Park SH, Blackstone C (2016) Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology. Exp Cell Res 349:32\u201344. https:\/\/doi.org\/10.1016\/j.yexcr.2016.09.015","journal-title":"Exp Cell Res"},{"key":"1088_CR76","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/ng758","volume":"29","author":"X Zhao","year":"2001","unstructured":"Zhao X, Alvarado D, Rainier S, Lemons R, Hedera P, Weber CH, Tukel T, Apak M, Heiman-Patterson T, Ming L et al (2001) Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia. Nat Genet 29:326\u2013331. https:\/\/doi.org\/10.1038\/ng758","journal-title":"Nat Genet"},{"key":"1088_CR77","doi-asserted-by":"publisher","first-page":"5638","DOI":"10.1093\/hmg\/ddu280","volume":"23","author":"PP Zhu","year":"2014","unstructured":"Zhu PP, Denton KR, Pierson TM, Li XJ, Blackstone C (2014) Pharmacologic rescue of axon growth defects in a human iPSC model of hereditary spastic paraplegia SPG3A. Hum Mol Genet 23:5638\u20135648. https:\/\/doi.org\/10.1093\/hmg\/ddu280","journal-title":"Hum Mol Genet"},{"key":"1088_CR78","doi-asserted-by":"publisher","first-page":"49063","DOI":"10.1074\/jbc.M306702200","volume":"278","author":"PP Zhu","year":"2003","unstructured":"Zhu PP, Patterson A, Lavoie B, Stadler J, Shoeb M, Patel R, Blackstone C (2003) Cellular localization, oligomerization, and membrane association of the hereditary spastic paraplegia 3A (SPG3A) protein atlastin. J Biol Chem 278:49063\u201349071. https:\/\/doi.org\/10.1074\/jbc.M306702200","journal-title":"J Biol Chem"},{"key":"1088_CR79","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1093\/hmg\/ddl054","volume":"15","author":"PP Zhu","year":"2006","unstructured":"Zhu PP, Soderblom C, Tao-Cheng JH, Stadler J, Blackstone C (2006) SPG3A protein atlastin-1 is enriched in growth cones and promotes axon elongation during neuronal development. Hum Mol Genet 15:1343\u20131353. https:\/\/doi.org\/10.1093\/hmg\/ddl054","journal-title":"Hum Mol Genet"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-020-01088-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s40478-020-01088-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-020-01088-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T21:33:04Z","timestamp":1618608784000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/s40478-020-01088-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":79,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1088"],"URL":"https:\/\/doi.org\/10.1186\/s40478-020-01088-0","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"8 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 December 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"214"}}