{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:25:11Z","timestamp":1778851511939,"version":"3.51.4"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2010,9,21]],"date-time":"2010-09-21T00:00:00Z","timestamp":1285027200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0012788","type":"journal-article","created":{"date-parts":[[2010,9,21]],"date-time":"2010-09-21T20:05:43Z","timestamp":1285099543000},"page":"e12788","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Cholesterol Pathways Affected by Small Molecules That Decrease Sterol Levels in Niemann-Pick Type C Mutant Cells"],"prefix":"10.1371","volume":"5","author":[{"given":"Madalina","family":"Rujoi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina H.","family":"Pipalia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick R.","family":"Maxfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2010,9,21]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/nature04399","article-title":"Role of cholesterol and lipid organization in disease.","volume":"438","author":"FR Maxfield","year":"2005","journal-title":"Nature"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.bbalip.2004.08.009","article-title":"Lipid and cholesterol trafficking in NPC.","volume":"1685","author":"S Mukherjee","year":"2004","journal-title":"Biochim Biophys Acta"},{"key":"ref3","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":"TY Chang","year":"2005","journal-title":"J Biol Chem"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.semcdb.2004.03.001","article-title":"Cellular pathology of Niemann-Pick type C disease.","volume":"15","author":"E Ikonen","year":"2004","journal-title":"Semin Cell Dev Biol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1098\/rstb.2003.1275","article-title":"Endocytic trafficking of glycosphingolipids in sphingolipid storage diseases.","volume":"358","author":"RE Pagano","year":"2003","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.bbalip.2004.08.014","article-title":"The pathophysiology and mechanisms of NP-C disease.","volume":"1685","author":"SL Sturley","year":"2004","journal-title":"Biochim Biophys Acta"},{"key":"ref7","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":"MT Vanier","year":"2003","journal-title":"Clin Genet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1126\/science.277.5323.228","article-title":"Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.","volume":"277","author":"ED Carstea","year":"1997","journal-title":"Science"},{"key":"ref9","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":"S Naureckiene","year":"2000","journal-title":"Science"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"9627","DOI":"10.1074\/jbc.274.14.9627","article-title":"The Niemann-Pick C1 protein resides in a vesicular compartment linked to retrograde transport of multiple lysosomal cargo.","volume":"274","author":"EB Neufeld","year":"1999","journal-title":"J Biol Chem"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1073\/pnas.96.4.1657","article-title":"Localization of Niemann-Pick C1 protein in astrocytes: implications for neuronal degeneration in Niemann- Pick type C disease.","volume":"96","author":"SC Patel","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/mgme.1999.2882","article-title":"Niemann-Pick C1 is a late endosome-resident protein that transiently associates with lysosomes and the trans-Golgi network.","volume":"68","author":"ME Higgins","year":"1999","journal-title":"Mol Genet Metab"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S1388-1981(99)00070-0","article-title":"A porcine homolog of the major secretory protein of human epididymis, HE1, specifically binds cholesterol.","volume":"1438","author":"N Okamura","year":"1999","journal-title":"Biochim Biophys Acta"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.tibs.2005.07.007","article-title":"Guilty until proven innocent: the case of NPC1 and cholesterol.","volume":"30","author":"YA Ioannou","year":"2005","journal-title":"Trends Biochem Sci"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bbalip.2004.08.008","article-title":"Intracellular trafficking of Niemann-Pick C proteins 1 and 2: obligate components of subcellular lipid transport.","volume":"1685","author":"L Liscum","year":"2004","journal-title":"Biochim Biophys Acta"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.bbalip.2004.08.006","article-title":"The NPC1 protein: structure implies function.","volume":"1685","author":"C Scott","year":"2004","journal-title":"Biochim Biophys Acta"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1651-2227.2003.tb00224.x","article-title":"Differential trafficking of the Niemann-Pick C1 and 2 proteins highlights distinct roles in late endocytic lipid trafficking.","volume":"Suppl 92","author":"M Zhang","year":"2003","journal-title":"Acta Paediatr"},{"key":"ref18","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":"EJ Blanchette-Mackie","year":"2000","journal-title":"Biochim Biophys Acta"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"12473","DOI":"10.1073\/pnas.0405255101","article-title":"Binding between the Niemann-Pick C1 protein and a photoactivatable cholesterol analog requires a functional sterol-sensing domain.","volume":"101","author":"N Ohgami","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"8247","DOI":"10.1073\/pnas.82.23.8247","article-title":"A defect in cholesterol esterification in Niemann-Pick disease (type C) patients.","volume":"82","author":"PG Pentchev","year":"1985","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"4013","DOI":"10.1074\/jbc.275.6.4013","article-title":"Role of Niemann-Pick type C1 protein in intracellular trafficking of low density lipoprotein-derived cholesterol.","volume":"275","author":"JC Cruz","year":"2000","journal-title":"J Biol Chem"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S1357-4310(98)01374-4","article-title":"Niemann-Pick C disease: cholesterol handling gone awry.","volume":"4","author":"JA Morris","year":"1998","journal-title":"Mol Med Today"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"17002","DOI":"10.1016\/S0021-9258(18)45483-X","article-title":"Low density lipoprotein (LDL)-mediated suppression of cholesterol synthesis and LDL uptake is defective in Niemann-Pick type C fibroblasts.","volume":"262","author":"L Liscum","year":"1987","journal-title":"J Biol Chem"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0076-6879(83)98152-1","article-title":"Receptor-mediated endocytosis of low-density lipoprotein in cultured cells.","volume":"98","author":"JL Goldstein","year":"1983","journal-title":"Methods Enzymol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"8487","DOI":"10.1016\/S0021-9258(19)40786-2","article-title":"Role of lysosomal acid lipase in the metabolism of plasma low density lipoprotein. Observations in cultured fibroblasts from a patient with cholesteryl ester storage disease.","volume":"250","author":"JL Goldstein","year":"1975","journal-title":"J Biol Chem"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1161\/01.ATV.0000068683.51375.59","article-title":"Role of ABCA1 in cellular cholesterol efflux and reverse cholesterol transport.","volume":"23","author":"AR Tall","year":"2003","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1146\/annurev.biochem.66.1.613","article-title":"Acyl-coenzyme A:cholesterol acyltransferase.","volume":"66","author":"TY Chang","year":"1997","journal-title":"Annu Rev Biochem"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cell.2005.12.022","article-title":"Protein sensors for membrane sterols.","volume":"124","author":"JL Goldstein","year":"2006","journal-title":"Cell"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1126\/science.3513311","article-title":"A receptor-mediated pathway for cholesterol homeostasis.","volume":"232","author":"MS Brown","year":"1986","journal-title":"Science"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"21604","DOI":"10.1074\/jbc.271.35.21604","article-title":"Intracellular trafficking of cholesterol monitored with a cyclodextrin.","volume":"271","author":"EB Neufeld","year":"1996","journal-title":"J Biol Chem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1083\/jcb.108.5.1625","article-title":"The intracellular transport of low density lipoprotein-derived cholesterol is defective in Niemann-Pick type C fibroblasts.","volume":"108","author":"L Liscum","year":"1989","journal-title":"J Cell Biol"},{"key":"ref32","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":"J Sokol","year":"1988","journal-title":"J Biol Chem"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1091\/mbc.E02-11-0725","article-title":"Human acyl-coenzyme A:cholesterol acyltransferase expressed in chinese hamster ovary cells: membrane topology and active site location.","volume":"14","author":"S Lin","year":"2003","journal-title":"Mol Biol Cell"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1096\/fasebj.1.1.3609608","article-title":"Group C Niemann-Pick disease: faulty regulation of low-density lipoprotein uptake and cholesterol storage in cultured fibroblasts.","volume":"1","author":"PG Pentchev","year":"1987","journal-title":"FASEB J"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"14850","DOI":"10.1074\/jbc.M300488200","article-title":"The transport of low density lipoprotein-derived cholesterol to the plasma membrane is defective in NPC1 cells.","volume":"278","author":"KM Wojtanik","year":"2003","journal-title":"J Biol Chem"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S0022-2275(20)38489-3","article-title":"Localization of lipoprotein unesterified cholesterol in nondenaturing gradient gels with filipin.","volume":"29","author":"M Lefevre","year":"1988","journal-title":"J Lipid Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0021-9258(18)48480-3","article-title":"Absorption and fluorescence spectra of polyene antibiotics in the presence of cholesterol.","volume":"267","author":"MA Castanho","year":"1992","journal-title":"J Biol Chem"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.bbalip.2004.08.013","article-title":"Therapy of Niemann-Pick disease, type C.","volume":"1685","author":"MC Patterson","year":"2004","journal-title":"Biochim Biophys Acta"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1194\/jlr.M500388-JLR200","article-title":"Automated microscopy screening for compounds that partially revert cholesterol accumulation in Niemann-Pick C cells.","volume":"47","author":"NH Pipalia","year":"2006","journal-title":"J Lipid Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1083\/jcb.110.2.295","article-title":"Isolation and characterization of Chinese hamster ovary cell mutants defective in intracellular low density lipoprotein-cholesterol trafficking.","volume":"110","author":"KM Cadigan","year":"1990","journal-title":"J Cell Biol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"7787","DOI":"10.1016\/S0021-9258(19)43901-X","article-title":"Regulation of cytosolic acetoacetyl coenzyme A thiolase, 3-hydroxy-3-methylglutaryl coenzyme A synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and mevalonate kinase by low density lipoprotein and by 25-hydroxycholesterol in Chinese hamster ovary cells.","volume":"255","author":"TY Chang","year":"1980","journal-title":"J Biol Chem"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.bbalip.2009.08.005","article-title":"Chemical screen to reduce sterol accumulation in Niemann-Pick C disease cells identifies novel lysosomal acid lipase inhibitors.","volume":"1791","author":"AI Rosenbaum","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0021-9258(17)38120-6","article-title":"Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase.","volume":"253","author":"MS Brown","year":"1978","journal-title":"J Biol Chem"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1083\/jcb.117.2.301","article-title":"Delivery of ligands from sorting endosomes to late endosomes occurs by maturation of sorting endosomes.","volume":"117","author":"KW Dunn","year":"1992","journal-title":"J Cell Biol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1161\/01.ATV.1.3.177","article-title":"Acetoacetylated lipoproteins used to distinguish fibroblasts from macrophages in vitro by fluorescence microscopy.","volume":"1","author":"RE Pitas","year":"1981","journal-title":"Arteriosclerosis"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"6494","DOI":"10.1021\/jm900707n","article-title":"Investigation of N-aryl-3-alkylidenepyrrolinones as potential Niemann-Pick type C disease therapeutics.","volume":"52","author":"CC Cosner","year":"2009","journal-title":"J Med Chem"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"17401","DOI":"10.1016\/S0021-9258(18)38172-9","article-title":"Sequence identity between the alpha 2-macroglobulin receptor and low density lipoprotein receptor-related protein suggests that this molecule is a multifunctional receptor.","volume":"265","author":"DK Strickland","year":"1990","journal-title":"J Biol Chem"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0014-5793(90)80530-V","article-title":"Evidence that the newly cloned low-density-lipoprotein receptor related protein (LRP) is the alpha 2-macroglobulin receptor.","volume":"276","author":"T Kristensen","year":"1990","journal-title":"FEBS Lett"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0005-2760(94)00190-A","article-title":"Translocation of both lysosomal LDL-derived cholesterol and plasma membrane cholesterol to the endoplasmic reticulum for esterification may require common cellular factors involved in cholesterol egress from the acidic compartments (lysosomes\/endosomes).","volume":"1254","author":"DM Spillane","year":"1995","journal-title":"Biochim Biophys Acta"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/343425a0","article-title":"Regulation of the mevalonate pathway.","volume":"343","author":"JL Goldstein","year":"1990","journal-title":"Nature"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/j.1600-0854.2006.00513.x","article-title":"Sterol, protein and lipid trafficking in Chinese hamster ovary cells with Niemann-Pick type C1 defect.","volume":"8","author":"NH Pipalia","year":"2007","journal-title":"Traffic"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"4889","DOI":"10.1016\/S0021-9258(18)42914-6","article-title":"Isolation and characterization of Chinese hamster ovary cells defective in the intracellular metabolism of low density lipoprotein-derived cholesterol.","volume":"267","author":"NK Dahl","year":"1992","journal-title":"J Biol Chem"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1083\/jcb.82.3.614","article-title":"alpha 2 Macroglobulin binding to the plasma membrane of cultured fibroblasts. Diffuse binding followed by clustering in coated regions.","volume":"82","author":"MC Willingham","year":"1979","journal-title":"J Cell Biol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"29024","DOI":"10.1074\/jbc.M304855200","article-title":"Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia.","volume":"278","author":"C Jones","year":"2003","journal-title":"J Biol Chem"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jneumeth.2007.09.002","article-title":"Partial blockage of sterol biosynthesis with a squalene synthase inhibitor in early postnatal Niemann-Pick type C npcnih null mice brains reduces neuronal cholesterol accumulation, abrogates astrogliosis, but may inhibit myelin maturation.","volume":"168","author":"PC Reid","year":"2008","journal-title":"J Neurosci Methods"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1161\/ATVBAHA.108.179283","article-title":"Role of HDL, ABCA1, and ABCG1 transporters in cholesterol efflux and immune responses.","volume":"30","author":"L Yvan-Charvet","year":"2010","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1146\/annurev.med.57.121304.131428","article-title":"Nuclear receptors in lipid metabolism: targeting the heart of dyslipidemia.","volume":"57","author":"SW Beaven","year":"2006","journal-title":"Annu Rev Med"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"32569","DOI":"10.1074\/jbc.M304553200","article-title":"Impaired ABCA1-dependent lipid efflux and hypoalphalipoproteinemia in human Niemann-Pick type C disease.","volume":"278","author":"HY Choi","year":"2003","journal-title":"J Biol Chem"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"25517","DOI":"10.1074\/jbc.M302588200","article-title":"NPC1 and NPC2 regulate cellular cholesterol homeostasis through generation of low density lipoprotein cholesterol-derived oxysterols.","volume":"278","author":"A Frolov","year":"2003","journal-title":"J Biol Chem"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"14470","DOI":"10.1523\/JNEUROSCI.4823-07.2007","article-title":"Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouse.","volume":"27","author":"JJ Repa","year":"2007","journal-title":"J Neurosci"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0012788","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T17:14:14Z","timestamp":1711818854000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0012788"}},"subtitle":[],"editor":[{"given":"James","family":"Keen","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2010,9,21]]},"references-count":60,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2010,9,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0012788","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9,21]]}}}