{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:09:58Z","timestamp":1780405798016,"version":"3.54.1"},"reference-count":58,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2007,8,1]],"date-time":"2007-08-01T00:00:00Z","timestamp":1185926400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T00:00:00Z","timestamp":1602806400000},"content-version":"vor","delay-in-days":4825,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Lipid Research"],"published-print":{"date-parts":[[2007,8]]},"DOI":"10.1194\/jlr.m700125-jlr200","type":"journal-article","created":{"date-parts":[[2007,5,3]],"date-time":"2007-05-03T17:04:04Z","timestamp":1178211844000},"page":"1710-1723","source":"Crossref","is-referenced-by-count":40,"title":["Receptor-mediated and bulk-phase endocytosis cause macrophage and cholesterol accumulation in Niemann-Pick C disease"],"prefix":"10.1016","volume":"48","author":[{"given":"Benny","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chonglun","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Turley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Dietschy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1194\/jlr.M700125-JLR200_bib1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev.ph.48.030186.001003","article-title":"Functional activities of hepatic lipoprotein receptors","volume":"48","author":"Havel","year":"1986","journal-title":"Annu. Rev. Physiol."},{"key":"10.1194\/jlr.M700125-JLR200_bib2","doi-asserted-by":"crossref","first-page":"10771","DOI":"10.1016\/S0021-9258(18)87014-4","article-title":"Opposing effects of apolipoproteins E and C on lipoprotein binding to low density lipoprotein receptor-related protein","volume":"265","author":"Kowal","year":"1990","journal-title":"J. Biol. Chem."},{"key":"10.1194\/jlr.M700125-JLR200_bib3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.devbrainres.2003.09.015","article-title":"Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse","volume":"146","author":"Quan","year":"2003","journal-title":"Dev. Brain Res."},{"key":"10.1194\/jlr.M700125-JLR200_bib4","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1194\/jlr.R400004-JLR200","article-title":"Cholesterol metabolism in the central nervous system during early development and in the mature animal","volume":"45","author":"Dietschy","year":"2004","journal-title":"J. Lipid Res."},{"key":"10.1194\/jlr.M700125-JLR200_bib5","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1161\/01.ATV.3.4.344","article-title":"Small liver fenestrae may explain the susceptibility of rabbits to atherosclerosis","volume":"3","author":"Wright","year":"1983","journal-title":"Arteriosclerosis."},{"key":"10.1194\/jlr.M700125-JLR200_bib6","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.1073\/pnas.91.10.4431","article-title":"The two-receptor model of lipoprotein clearance: tests of the hypothesis in \u201cknockout\u201d mice lacking the low density lipoprotein receptor, apolipoprotein E, or both proteins","volume":"91","author":"Ishibashi","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"10.1194\/jlr.M700125-JLR200_bib7","doi-asserted-by":"crossref","first-page":"12500","DOI":"10.1073\/pnas.92.26.12500","article-title":"Apolipoprotein E competitively inhibits receptor-dependent low density lipoprotein uptake by the liver but has no effect on cholesterol absorption or synthesis in the mouse","volume":"92","author":"Woollett","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"10.1194\/jlr.M700125-JLR200_bib8","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1126\/science.1078124","article-title":"Structure of the LDL receptor extracellular domain at endosomal pH","volume":"298","author":"Rudenko","year":"2002","journal-title":"Science."},{"key":"10.1194\/jlr.M700125-JLR200_bib9","doi-asserted-by":"crossref","first-page":"36710","DOI":"10.1074\/jbc.M608743200","article-title":"NPC2, the protein deficient in Niemann-Pick C2 disease, consists of multiple glycoforms that bind a variety of sterols","volume":"281","author":"Liou","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1194\/jlr.M700125-JLR200_bib10","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1126\/science.290.5500.2298","article-title":"Identification of HE1 as the second gene of Niemann-Pick C disease","volume":"290","author":"Naureckiene","year":"2000","journal-title":"Science."},{"key":"10.1194\/jlr.M700125-JLR200_bib11","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1126\/science.277.5323.232","article-title":"Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene","volume":"277","author":"Loftus","year":"1997","journal-title":"Science."},{"key":"10.1194\/jlr.M700125-JLR200_bib14","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.bbalip.2004.08.011","article-title":"Consequences of NPC1 and NPC2 loss of function in mammalian neurons","volume":"1685","author":"Walkley","year":"2004","journal-title":"Biochim. Biophys. Acta."},{"key":"10.1194\/jlr.M700125-JLR200_bib15","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1146\/annurev.cellbio.16.1.459","article-title":"The role of orphan nuclear receptors in the regulation of cholesterol homeostasis","volume":"16","author":"Repa","year":"2000","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"10.1194\/jlr.M700125-JLR200_bib16","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1172\/JCI0215593","article-title":"SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver","volume":"109","author":"Horton","year":"2002","journal-title":"J. Clin. Invest."},{"key":"10.1194\/jlr.M700125-JLR200_bib17","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1172\/JCI117760","article-title":"Role of the low density lipoprotein receptor in the flux of cholesterol through the plasma and across the tissues of the mouse","volume":"95","author":"Osono","year":"1995","journal-title":"J. Clin. Invest."},{"key":"10.1194\/jlr.M700125-JLR200_bib18","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0022-2275(20)37988-8","article-title":"Cholesterol synthesis in vivo and in vitro in the WHHL rabbit, an animal with defective low density lipoprotein receptors","volume":"24","author":"Dietschy","year":"1983","journal-title":"J. Lipid Res."},{"key":"10.1194\/jlr.M700125-JLR200_bib19","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S0022-2275(20)31157-3","article-title":"Lysosomal acid lipase-deficient mice: depletion of white and brown fat, severe hepatosplenomegaly, and shortened life span","volume":"42","author":"Du","year":"2001","journal-title":"J. Lipid Res."},{"key":"10.1194\/jlr.M700125-JLR200_bib20","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1093\/hmg\/7.9.1347","article-title":"Targeted disruption of the mouse lysosomal acid lipase gene: long-term survival with massive cholesteryl ester and triglyceride storage","volume":"7","author":"Du","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"10.1194\/jlr.M700125-JLR200_bib21","first-page":"E336","article-title":"Cholesterol balance and metabolism in mice with loss of function of Niemann-Pick C protein","volume":"276","author":"Xie","year":"1999","journal-title":"Am. J. Physiol."},{"key":"10.1194\/jlr.M700125-JLR200_bib22","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/S0022-2275(20)35728-X","article-title":"Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans","volume":"34","author":"Dietschy","year":"1993","journal-title":"J. Lipid Res."},{"key":"10.1194\/jlr.M700125-JLR200_bib23","doi-asserted-by":"crossref","first-page":"11992","DOI":"10.1073\/pnas.96.21.11992","article-title":"Cholesterol accumulation in tissues of the Niemann-Pick type C mouse is determined by the rate of lipoprotein-cholesterol uptake through the coated-pit pathway in each organ","volume":"96","author":"Xie","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"10.1194\/jlr.M700125-JLR200_bib24","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1194\/jlr.M500534-JLR200","article-title":"Cholesterol substrate pools and steroid hormone levels are normal in the face of mutational inactivation of NPC1 protein","volume":"47","author":"Xie","year":"2006","journal-title":"J. Lipid Res."},{"key":"10.1194\/jlr.M700125-JLR200_bib25","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1172\/JCI116663","article-title":"Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery","volume":"92","author":"Ishibashi","year":"1993","journal-title":"J. Clin. Invest."},{"key":"10.1194\/jlr.M700125-JLR200_bib26","doi-asserted-by":"crossref","first-page":"7161","DOI":"10.1016\/S0021-9258(18)32346-9","article-title":"Tissue sites of degradation of apoprotein A-I in the rat","volume":"258","author":"Glass","year":"1983","journal-title":"J. Biol. Chem."},{"key":"10.1194\/jlr.M700125-JLR200_bib27","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1042\/bj2120791","article-title":"A radioiodinated, intracellularly trapped ligand for determining the sites of plasma protein degradation in vivo","volume":"212","author":"Pittman","year":"1983","journal-title":"Biochem. J."},{"key":"10.1194\/jlr.M700125-JLR200_bib28","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/S0022-2275(20)39811-4","article-title":"Subfractionation of human high density lipoprotein by heparin-Sepharose affinity chromatography","volume":"21","author":"Weisgraber","year":"1980","journal-title":"J. Lipid Res."},{"key":"10.1194\/jlr.M700125-JLR200_bib29","doi-asserted-by":"crossref","first-page":"9053","DOI":"10.1016\/S0021-9258(17)34284-9","article-title":"Role of the lysine residues of plasma lipoproteins in high affinity binding to cell surface receptors on human fibroblasts","volume":"253","author":"Weisgraber","year":"1978","journal-title":"J. Biol. Chem."},{"key":"10.1194\/jlr.M700125-JLR200_bib30","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.1073\/pnas.80.11.3499","article-title":"Rates of receptor-dependent and -independent low density lipoprotein uptake in the hamster","volume":"80","author":"Spady","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"10.1194\/jlr.M700125-JLR200_bib31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0022-2275(20)39755-8","article-title":"Role of liver in the synthesis of cholesterol and the clearance of low density lipoproteins in the cynomolgus monkey","volume":"36","author":"Turley","year":"1995","journal-title":"J. Lipid Res."},{"key":"10.1194\/jlr.M700125-JLR200_bib33","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/hep.20868","article-title":"Cholesterol accumulation and liver cell death in the mouse with Niemann-Pick type C disease","volume":"42","author":"Beltroy","year":"2005","journal-title":"Hepatology."},{"key":"10.1194\/jlr.M700125-JLR200_bib34","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1172\/JCI112460","article-title":"Kinetic constants for receptor-dependent and receptor-independent low density lipoprotein transport in the tissues of the rat and hamster","volume":"77","author":"Spady","year":"1986","journal-title":"J. Clin. Invest."},{"key":"10.1194\/jlr.M700125-JLR200_bib35","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S0022-2275(20)38731-9","article-title":"Role of receptor-independent low density lipoprotein transport in the maintenance of tissue cholesterol balance in the normal and WHHL rabbit","volume":"28","author":"Spady","year":"1987","journal-title":"J. Lipid Res."},{"key":"10.1194\/jlr.M700125-JLR200_bib36","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1113\/jphysiol.1973.sp010086","article-title":"Blood volume determination in the mouse","volume":"228","author":"Riches","year":"1973","journal-title":"J. Physiol."},{"key":"10.1194\/jlr.M700125-JLR200_bib37","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1194\/jlr.M600488-JLR200","article-title":"Lysosomal unesterified cholesterol content correlates with liver cell death in murine Niemann-Pick type C disease","volume":"48","author":"Beltroy","year":"2007","journal-title":"J. Lipid Res."},{"key":"10.1194\/jlr.M700125-JLR200_bib38","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1093\/jnen\/59.12.1106","article-title":"Cholesterol is sequestered in the brains of mice with Niemann-Pick type C disease but turnover is increased","volume":"59","author":"Xie","year":"2000","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1194\/jlr.M700125-JLR200_bib39","doi-asserted-by":"crossref","unstructured":"Mieli-Vergani, G., E. R. Howard, and A. P. Mowat. 1991. Liver disease in infancy: a 20 year perspective. Gut. (Suppl.): 123\u2013128.","DOI":"10.1136\/gut.32.Suppl.S123"},{"key":"10.1194\/jlr.M700125-JLR200_bib41","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s10072-005-0456-z","article-title":"Lung involvement in Niemann-Pick disease type C1: improvement with bronchoalveolar lavage","volume":"26","author":"Palmeri","year":"2005","journal-title":"Neurol. Sci."},{"key":"10.1194\/jlr.M700125-JLR200_bib42","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1750-3639.1998.tb00143.x","article-title":"Recent advances in elucidating Niemann-Pick C disease","volume":"8","author":"Vanier","year":"1998","journal-title":"Brain Pathol."},{"key":"10.1194\/jlr.M700125-JLR200_bib43","doi-asserted-by":"crossref","first-page":"20917","DOI":"10.1074\/jbc.R400040200","article-title":"Niemann-Pick type C disease and intracellular cholesterol trafficking","volume":"280","author":"Chang","year":"2005","journal-title":"J. Biol. Chem."},{"key":"10.1194\/jlr.M700125-JLR200_bib44","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1034\/j.1399-0004.2003.00147.x","article-title":"Niemann-Pick disease type C","volume":"64","author":"Vanier","year":"2003","journal-title":"Clin. Genet."},{"key":"10.1194\/jlr.M700125-JLR200_bib45","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/jnen\/64.4.323","article-title":"Molecular, anatomical, and biochemical events associated with neurodegeneration in mice with Niemann-Pick type C disease","volume":"64","author":"Li","year":"2005","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1194\/jlr.M700125-JLR200_bib46","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1523\/JNEUROSCI.5282-06.2007","volume":"27","author":"Suzuki","year":"2007","journal-title":"J. Neurosci."},{"key":"10.1194\/jlr.M700125-JLR200_bib47","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1073\/pnas.76.7.3330","article-title":"Receptor-mediated endocytosis: insights from the lipoprotein receptor system","volume":"76","author":"Brown","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"10.1194\/jlr.M700125-JLR200_bib49","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev.biochem.71.110601.135342","article-title":"Lipoprotein receptors in the nervous system","volume":"71","author":"Herz","year":"2002","journal-title":"Annu. Rev. Biochem."},{"key":"10.1194\/jlr.M700125-JLR200_bib50","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1016\/S0022-2275(20)37560-X","article-title":"Brain does not utilize low density lipoprotein-cholesterol during fetal and neonatal development in the sheep","volume":"37","author":"Turley","year":"1996","journal-title":"J. Lipid Res."},{"key":"10.1194\/jlr.M700125-JLR200_bib51","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1194\/jlr.R300017-JLR200","article-title":"Functions of lipoprotein receptors in neurons","volume":"45","author":"Beffert","year":"2004","journal-title":"J. Lipid Res."},{"key":"10.1194\/jlr.M700125-JLR200_bib53","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/bies.10195","article-title":"Outsourcing in the brain: do neurons depend on cholesterol delivery by astrocytes?","volume":"25","author":"Pfrieger","year":"2003","journal-title":"Bioessays."},{"key":"10.1194\/jlr.M700125-JLR200_bib54","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/cne.1149","article-title":"Selective neurodegeneration, without neurofibrillary tangles, in a mouse model of Niemann-Pick C disease","volume":"433","author":"German","year":"2001","journal-title":"J. Comp. Neurol."},{"key":"10.1194\/jlr.M700125-JLR200_bib55","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0306-4522(01)00517-6","article-title":"Neurodegeneration in the Niemann-Pick C mouse: glial involvement","volume":"109","author":"German","year":"2002","journal-title":"Neuroscience."},{"key":"10.1194\/jlr.M700125-JLR200_bib56","series-title":"The Metabolic and Molecular Bases of Inherited Diseases","first-page":"2625","article-title":"Niemann-Pick disease type C: a cellular cholesterol lipidosis","author":"Pentchev","year":"1995"},{"key":"10.1194\/jlr.M700125-JLR200_bib58","doi-asserted-by":"crossref","first-page":"8022","DOI":"10.1073\/pnas.85.21.8022","article-title":"Type-C Niemann-Pick disease: low density lipoprotein uptake is associated with premature cholesterol accumulation in the Golgi complex and excessive cholesterol storage in lysosomes","volume":"85","author":"Blanchette-Mackie","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"10.1194\/jlr.M700125-JLR200_bib12","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S1388-1981(00)00055-X","article-title":"Intracellular cholesterol trafficking: role of the NPC1 protein","volume":"1486","author":"Blanchette-Mackie","year":"2000","journal-title":"Biochim. Biophys. Acta."},{"key":"10.1194\/jlr.M700125-JLR200_bib13","doi-asserted-by":"crossref","first-page":"31594","DOI":"10.1074\/jbc.M602765200","article-title":"Mechanism of cholesterol transfer from the Niemann-Pick type C2 protein to model membranes supports a role in lysosomal cholesterol transport","volume":"281","author":"Cheruku","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1194\/jlr.M700125-JLR200_bib32","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1007\/BF02535281","article-title":"Rapid separation of neutral lipids, free fatty acids and polar lipids using prepacked silica Sep-Pak columns","volume":"23","author":"Hamilton","year":"1988","journal-title":"Lipids."},{"key":"10.1194\/jlr.M700125-JLR200_bib40","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S0022-3476(05)81695-6","article-title":"Niemann-Pick disease type C: diagnosis and outcome in children, with particular reference to liver disease","volume":"123","author":"Kelly","year":"1993","journal-title":"J. Pediatr."},{"key":"10.1194\/jlr.M700125-JLR200_bib48","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1021\/bi00601a013","article-title":"Enhanced binding by cultured human fibroblasts of apo-E-containing lipoproteins as compared with low density lipoproteins","volume":"17","author":"Innerarity","year":"1978","journal-title":"Biochemistry."},{"key":"10.1194\/jlr.M700125-JLR200_bib52","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1126\/science.294.5545.1354","article-title":"CNS synaptogenesis promoted by glia-derived cholesterol","volume":"294","author":"Mauch","year":"2001","journal-title":"Science."},{"key":"10.1194\/jlr.M700125-JLR200_bib57","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1016\/S0021-9258(18)69086-6","article-title":"Type C Niemann-Pick disease. Lysosomal accumulation and defective intracellular mobilization of low density lipoprotein cholesterol","volume":"263","author":"Sokol","year":"1988","journal-title":"J. Biol. Chem."}],"container-title":["Journal of Lipid Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022227520425076?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022227520425076?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1194\/jlr.M700125-JLR200","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,20]],"date-time":"2021-11-20T23:19:10Z","timestamp":1637450350000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022227520425076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8]]},"references-count":58,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2007,8]]}},"alternative-id":["S0022227520425076"],"URL":"https:\/\/doi.org\/10.1194\/jlr.m700125-jlr200","relation":{},"ISSN":["0022-2275"],"issn-type":[{"value":"0022-2275","type":"print"}],"subject":[],"published":{"date-parts":[[2007,8]]}}}