{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T07:01:54Z","timestamp":1793948514967,"version":"4.8.0"},"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K15487"],"award-info":[{"award-number":["17K15487"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP17H03996"],"award-info":[{"award-number":["JP17H03996"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Niemann-Pick disease type C is a rare, fatal neurodegenerative disorder characterized by massive intracellular accumulation of cholesterol. In most cases, loss-of-function mutations in the<jats:italic>NPC1<\/jats:italic>gene that encodes lysosomal cholesterol transporter NPC1 are responsible for the disease, and more than half of the mutations are considered to interfere with the biogenesis or folding of the protein. We previously identified a series of oxysterol derivatives and phenanthridine-6-one derivatives as pharmacological chaperones, i.e., small molecules that can rescue folding-defective phenotypes of mutated NPC1, opening up an avenue to develop chaperone therapy for Niemann-Pick disease type C. Here, we present an improved image-based screen for NPC1 chaperones and we describe its application for drug-repurposing screening. We identified some azole antifungals, including itraconazole and posaconazole, and a kinase inhibitor, lapatinib, as probable pharmacological chaperones. A photo-crosslinking study confirmed direct binding of itraconazole to a representative folding-defective mutant protein, NPC1-I1061T. Competitive photo-crosslinking experiments suggested that oxysterol-based chaperones and itraconazole share the same or adjacent binding site(s), and the sensitivity of the crosslinking to P691S mutation in the sterol-sensing domain supports the hypothesis that their binding sites are located near this domain. Although the azoles were less effective in reducing cholesterol accumulation than the oxysterol-derived chaperones or an HDAC inhibitor, LBH-589, our findings should offer new starting points for medicinal chemistry efforts to develop better pharmacological chaperones for NPC1.<\/jats:p>","DOI":"10.1371\/journal.pone.0243746","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T18:41:21Z","timestamp":1607971281000},"page":"e0243746","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Image-based screen capturing misfolding status of Niemann-Pick type C1 identifies potential candidates for chaperone drugs"],"prefix":"10.1371","volume":"15","author":[{"given":"Ryuta","family":"Shioi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3815-713X","authenticated-orcid":true,"given":"Fumika","family":"Karaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9281-9982","authenticated-orcid":true,"given":"Hiromasa","family":"Yoshioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Noguchi-Yachide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6008-2915","authenticated-orcid":true,"given":"Kosuke","family":"Dodo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikiko","family":"Sodeoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0565-6503","authenticated-orcid":true,"given":"Kenji","family":"Ohgane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,14]]},"reference":[{"key":"pone.0243746.ref001","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":"pone.0243746.ref002","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":"SK Loftus","year":"1997","journal-title":"Science"},{"key":"pone.0243746.ref003","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":"pone.0243746.ref004","doi-asserted-by":"crossref","first-page":"24367","DOI":"10.1074\/jbc.M002184200","article-title":"Topological analysis of Niemann-Pick C1 protein reveals that the membrane orientation of the putative sterol-sensing domain is identical to those of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element binding protein cleavage-activating protein","volume":"275","author":"JP Davies","year":"2000","journal-title":"J Biol Chem"},{"key":"pone.0243746.ref005","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.bbalip.2009.02.001","article-title":"Niemann-Pick C2 (NPC2) and intracellular cholesterol trafficking","volume":"1791","author":"J Storch","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"pone.0243746.ref006","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.cmet.2010.05.016","article-title":"Identification of Surface Residues on Niemann-Pick C2 Essential for Hydrophobic Handoff of Cholesterol to NPC1 in Lysosomes","volume":"12","author":"ML Wang","year":"2010","journal-title":"Cell metabolism"},{"key":"pone.0243746.ref007","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1074\/jbc.TM118.004165","article-title":"NPC intracellular cholesterol transporter 1 (NPC1)-mediated cholesterol export from lysosomes","volume":"294","author":"SR Pfeffer","year":"2019","journal-title":"J Biol Chem"},{"key":"pone.0243746.ref008","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.cell.2019.08.038","article-title":"Structural Insight into Eukaryotic Sterol Transport through Niemann-Pick Type C Proteins","volume":"179","author":"MBL Winkler","year":"2019","journal-title":"Cell"},{"key":"pone.0243746.ref009","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1136\/jmg.37.9.707","article-title":"Genotype-phenotype relationship of Niemann-Pick disease type C: a possible correlation between clinical onset and levels of NPC1 protein in isolated skin fibroblasts","volume":"37","author":"T Yamamoto","year":"2000","journal-title":"J Med Genet"},{"key":"pone.0243746.ref010","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0387-7604(03)00162-1","article-title":"Increased NPC1 mRNA in skin fibroblasts from Niemann-Pick disease type C patients","volume":"26","author":"T Yamamoto","year":"2004","journal-title":"Brain Dev"},{"key":"pone.0243746.ref011","doi-asserted-by":"crossref","first-page":"5292","DOI":"10.1038\/s41598-019-41707-y","article-title":"Different Niemann-Pick C1 Genotypes Generate Protein Phenotypes that Vary in their Intracellular Processing, Trafficking and Localization","volume":"9","author":"H Shammas","year":"2019","journal-title":"Sci Rep"},{"key":"pone.0243746.ref012","article-title":"Individualized Management of Genetic Diversity in Niemann-Pick C1 through Modulation of the Hsp70 Chaperone System","author":"C Wang","year":"2019","journal-title":"Hum Mol Genet"},{"key":"pone.0243746.ref013","doi-asserted-by":"crossref","first-page":"8229","DOI":"10.1074\/jbc.M708735200","article-title":"Niemann-Pick type C1 I1061T mutant encodes a functional protein that is selected for endoplasmic reticulum-associated degradation due to protein misfolding","volume":"283","author":"ME Gelsthorpe","year":"2008","journal-title":"J Biol Chem"},{"key":"pone.0243746.ref014","doi-asserted-by":"crossref","first-page":"19714","DOI":"10.1074\/jbc.M114.549915","article-title":"Endoplasmic reticulum-associated degradation of Niemann-Pick C1: evidence for the role of heat shock proteins and identification of lysine residues that accept ubiquitin","volume":"289","author":"N Nakasone","year":"2014","journal-title":"J Biol Chem"},{"key":"pone.0243746.ref015","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1074\/jbc.272.2.709","article-title":"Correction of defective protein kinesis of human P-glycoprotein mutants by substrates and modulators","volume":"272","author":"TW Loo","year":"1997","journal-title":"J Biol Chem"},{"key":"pone.0243746.ref016","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1172\/JCI8688","article-title":"Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants","volume":"105","author":"JP Morello","year":"2000","journal-title":"J Clin Invest"},{"key":"pone.0243746.ref017","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1006\/bbrc.1993.2659","article-title":"Characterization of a mutant alpha-galactosidase gene product for the late-onset cardiac form of Fabry disease","volume":"197","author":"S Ishii","year":"1993","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0243746.ref018","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/4801","article-title":"Accelerated transport and maturation of lysosomal alpha-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor","volume":"5","author":"JQ Fan","year":"1999","journal-title":"Nat Med"},{"key":"pone.0243746.ref019","doi-asserted-by":"crossref","first-page":"18843","DOI":"10.1073\/pnas.1105787108","article-title":"Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809","volume":"108","author":"F Van Goor","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0243746.ref020","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.chembiol.2013.02.009","article-title":"Discovery of oxysterol-derived pharmacological chaperones for NPC1: implication for the existence of second sterol-binding site","volume":"20","author":"K Ohgane","year":"2013","journal-title":"Chem Biol"},{"key":"pone.0243746.ref021","doi-asserted-by":"crossref","first-page":"3480","DOI":"10.1016\/j.bmcl.2014.05.064","article-title":"Structure-activity relationships of oxysterol-derived pharmacological chaperones for Niemann-Pick type C1 protein","volume":"24","author":"K Ohgane","year":"2014","journal-title":"Bioorg Med Chem Lett"},{"key":"pone.0243746.ref022","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.1016\/j.bmcl.2017.04.062","article-title":"Phenanthridin-6-one derivatives as the first class of non-steroidal pharmacological chaperones for Niemann-Pick disease type C1 protein","volume":"27","author":"H Fukuda","year":"2017","journal-title":"Bioorg Med Chem Lett"},{"key":"pone.0243746.ref023","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/nm.3595","article-title":"Overcoming Drug Development Bottlenecks With Repurposing: Old drugs learn new tricks","volume":"20","author":"SM Strittmatter","year":"2014","journal-title":"Nat Med"},{"key":"pone.0243746.ref024","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1093\/bioinformatics\/btq046","article-title":"EBImage\u2014an R package for image processing with applications to cellular phenotypes","volume":"26","author":"G Pau","year":"2010","journal-title":"Bioinformatics"},{"key":"pone.0243746.ref025","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/cyto.a.20258","article-title":"A new \u201cLogicle\u201d display method avoids deceptive effects of logarithmic scaling for low signals and compensated data","volume":"69","author":"DR Parks","year":"2006","journal-title":"Cytometry A"},{"key":"pone.0243746.ref026","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ab.2011.01.038","article-title":"High-resolution Native-PAGE for membrane proteins capable of fluorescence detection and hydrodynamic state evaluation","volume":"412","author":"M Ihara","year":"2011","journal-title":"Anal Biochem"},{"key":"pone.0243746.ref027","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ab.2003.10.047","article-title":"Visible fluorescent detection of proteins in polyacrylamide gels without staining","volume":"326","author":"CL Ladner","year":"2004","journal-title":"Anal Biochem"},{"key":"pone.0243746.ref028","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1091\/mbc.E17-08-0514","article-title":"A VCP inhibitor substrate trapping approach (VISTA) enables proteomic profiling of endogenous ERAD substrates","volume":"29","author":"EY Huang","year":"2018","journal-title":"Mol Biol Cell"},{"key":"pone.0243746.ref029","doi-asserted-by":"crossref","first-page":"52479","DOI":"10.1074\/jbc.M310053200","article-title":"Insig-dependent ubiquitination and degradation of mammalian 3-hydroxy-3-methylglutaryl-CoA reductase stimulated by sterols and geranylgeraniol","volume":"278","author":"N Sever","year":"2003","journal-title":"J Biol Chem"},{"key":"pone.0243746.ref030","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/9780470559277.ch090167","article-title":"Target Identification by Diazirine Photo-Cross-linking and Click Chemistry","volume":"1","author":"AL MacKinnon","year":"2009","journal-title":"Current Protocols in Chemical Biology"},{"key":"pone.0243746.ref031","article-title":"Quantification of Gel Bands by an Image J Macro, Band\/Peak Quantification Tool. protocols.io","author":"K Ohgane","year":"2019"},{"key":"pone.0243746.ref032","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/108705719900400206","article-title":"A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays","volume":"4","author":"J Zhang","year":"1999","journal-title":"J Biomol Screen"},{"key":"pone.0243746.ref033","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-1-60327-258-2_4","article-title":"Statistics and decision making in high-throughput screening","volume":"565","author":"I Coma","year":"2009","journal-title":"Methods Mol Biol"},{"key":"pone.0243746.ref034","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1242\/jcs.115.14.2907","article-title":"The cellular fate of mutant rhodopsin: quality control, degradation and aggresome formation","volume":"115","author":"RS Saliba","year":"2002","journal-title":"J Cell Sci"},{"issue":"41","key":"pone.0243746.ref035","doi-asserted-by":"crossref","first-page":"25710","DOI":"10.1016\/S0021-9258(18)47306-1","article-title":"Intracellular turnover of cystic fibrosis transmembrane conductance regulator. Inefficient processing and rapid degradation of wild-type and mutant proteins","volume":"269","author":"CL Ward","year":"1994","journal-title":"J Biol Chem"},{"issue":"6","key":"pone.0243746.ref036","first-page":"94","article-title":"SuperPlots: Communicating reproducibility and variability in cell biology","volume":"219","author":"SJ Lord","year":"2020","journal-title":"J Cell Biol"},{"key":"pone.0243746.ref037","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1074\/mcp.M700076-MCP200","article-title":"High resolution clear native electrophoresis for in-gel functional assays and fluorescence studies of membrane protein complexes","volume":"6","author":"I Wittig","year":"2007","journal-title":"Molecular & Cellular Proteomics"},{"key":"pone.0243746.ref038","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.str.2006.01.013","article-title":"Fluorescence-detection size-exclusion chromatography for precrystallization screening of integral membrane proteins","volume":"14","author":"T Kawate","year":"2006","journal-title":"Structure"},{"key":"pone.0243746.ref039","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ab.2018.02.007","article-title":"An efficient screening method for purifying and crystallizing membrane proteins using modified clear-native PAGE","volume":"548","author":"N Suzuki","year":"2018","journal-title":"Anal Biochem"},{"key":"pone.0243746.ref040","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ab.2012.09.012","article-title":"Analysis of the phospholipase C-\u03b41 pleckstrin homology domain using native polyacrylamide gel electrophoresis","volume":"431","author":"M Tanio","year":"2012","journal-title":"Anal Biochem"},{"key":"pone.0243746.ref041","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.str.2012.06.009","article-title":"A fluorescence-detection size-exclusion chromatography-based thermostability assay for membrane protein precrystallization screening","volume":"20","author":"M Hattori","year":"2012","journal-title":"Structure"},{"key":"pone.0243746.ref042","doi-asserted-by":"crossref","first-page":"44045","DOI":"10.1074\/jbc.M111.278754","article-title":"The antifungal drug itraconazole inhibits vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, trafficking, and signaling in endothelial cells","volume":"286","author":"BA Nacev","year":"2011","journal-title":"J Biol Chem"},{"key":"pone.0243746.ref043","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/j.bmcl.2005.01.041","article-title":"Design of dantrolene-derived probes for radioisotope-free photoaffinity labeling of proteins involved in the physiological Ca2+ release from sarcoplasmic reticulum of skeletal muscle","volume":"15","author":"T Hosoya","year":"2005","journal-title":"Bioorg Med Chem Lett"},{"key":"pone.0243746.ref044","doi-asserted-by":"crossref","first-page":"14609","DOI":"10.1021\/jacs.6b06645","article-title":"2-Aryl-5-carboxytetrazole as a New Photoaffinity Label for Drug Target Identification","volume":"138","author":"A Herner","year":"2016","journal-title":"J Am Chem Soc"},{"key":"pone.0243746.ref045","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nchembio.765","article-title":"Oxysterols are allosteric activators of the oncoprotein Smoothened","volume":"8","author":"S Nachtergaele","year":"2012","journal-title":"Nat Chem Biol"},{"key":"pone.0243746.ref046","doi-asserted-by":"crossref","first-page":"9879","DOI":"10.1002\/anie.200905087","article-title":"Analysis and optimization of copper-catalyzed azide-alkyne cycloaddition for bioconjugation","volume":"48","author":"V Hong","year":"2009","journal-title":"Angew Chem Int Ed Engl"},{"key":"pone.0243746.ref047","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1021\/acschembio.6b00849","article-title":"Simultaneous Targeting of NPC1 and VDAC1 by Itraconazole Leads to Synergistic Inhibition of mTOR Signaling and Angiogenesis","volume":"12","author":"SA Head","year":"2017","journal-title":"ACS Chem Biol"},{"key":"pone.0243746.ref048","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1073\/pnas.1619571114","article-title":"Triazoles inhibit cholesterol export from lysosomes by binding to NPC1","volume":"114","author":"MN Trinh","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0243746.ref049","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 USA"},{"key":"pone.0243746.ref050","unstructured":"Karaki F. [Application of pharmacological chaperone effect in identifying and developing novel NPC1L1 ligands] (in Japanese). Ph.D. Thesis, The University of Tokyo. 2014. Available from: http:\/\/doi.org\/10.15083\/00007033"},{"key":"pone.0243746.ref051","first-page":"19316","article-title":"Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection","volume":"4","author":"F Lu","year":"2015","journal-title":"Elife"},{"key":"pone.0243746.ref052","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1074\/jbc.M707943200","article-title":"Purified NPC1 protein. I. Binding of cholesterol and oxysterols to a 1278-amino acid membrane protein","volume":"283","author":"RE Infante","year":"2008","journal-title":"J Biol Chem"},{"key":"pone.0243746.ref053","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1074\/jbc.M707944200","article-title":"Purified NPC1 protein: II. Localization of sterol binding to a 240-amino acid soluble luminal loop","volume":"283","author":"RE Infante","year":"2008","journal-title":"J Biol Chem"},{"key":"pone.0243746.ref054","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.cell.2009.03.049","article-title":"Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol","volume":"137","author":"HJ Kwon","year":"2009","journal-title":"Cell"},{"key":"pone.0243746.ref055","doi-asserted-by":"crossref","first-page":"15330","DOI":"10.1073\/pnas.1112751108","article-title":"Amino acid substitution in NPC1 that abolishes cholesterol binding reproduces phenotype of complete NPC1 deficiency in mice","volume":"108","author":"X Xie","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0243746.ref056","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/bs.mcb.2014.10.028","article-title":"Laboratory diagnosis of Niemann-Pick disease type C: the filipin staining test","volume":"126","author":"MT Vanier","year":"2015","journal-title":"Methods Cell Biol"},{"key":"pone.0243746.ref057","doi-asserted-by":"crossref","first-page":"15428","DOI":"10.1073\/pnas.192582899","article-title":"Chemical chaperones increase the cellular activity of N370S beta -glucosidase: a therapeutic strategy for Gaucher disease","volume":"99","author":"AR Sawkar","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0243746.ref058","doi-asserted-by":"crossref","first-page":"23842","DOI":"10.1074\/jbc.M111.227645","article-title":"An \u201cexacerbate-reverse\u201d strategy in yeast identifies histone deacetylase inhibition as a correction for cholesterol and sphingolipid transport defects in human Niemann-Pick type C disease","volume":"286","author":"AB Munkacsi","year":"2011","journal-title":"J Biol Chem"},{"key":"pone.0243746.ref059","doi-asserted-by":"crossref","first-page":"5620","DOI":"10.1073\/pnas.1014890108","article-title":"Histone deacetylase inhibitor treatment dramatically reduces cholesterol accumulation in Niemann-Pick type C1 mutant human fibroblasts","volume":"108","author":"NH Pipalia","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0243746.ref060","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.1093\/hmg\/dds145","article-title":"Ryanodine receptor antagonists adapt NPC1 proteostasis to ameliorate lipid storage in Niemann-Pick type C disease fibroblasts","volume":"21","author":"T Yu","year":"2012","journal-title":"Hum Mol Genet"},{"key":"pone.0243746.ref061","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1093\/hmg\/ddy117","article-title":"High-content screen for modifiers of Niemann-Pick type C disease in patient cells","volume":"27","author":"EK Pugach","year":"2018","journal-title":"Hum Mol Genet"},{"key":"pone.0243746.ref062","unstructured":"Ohgane K and Sodeoka M. Niemann-Pick disease type C preventive and\/or therapeutic agent. Published: Japan patent JP-2017-105738A \/ Application: JP-2015-242513A. Available from: https:\/\/www.j-platpat.inpit.go.jp\/c1800\/PU\/JP-2017-105738\/E9E8C20F179CD6EB9740623D6AF6FA6453108FA48A184812188FD420BDDE3BFC\/11\/ja"},{"key":"pone.0243746.ref063","doi-asserted-by":"crossref","first-page":"14876","DOI":"10.1073\/pnas.1520490112","article-title":"Glycosylation inhibition reduces cholesterol accumulation in NPC1 protein-deficient cells","volume":"112","author":"J Li","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0243746.ref064","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.brainres.2016.03.035","article-title":"Lysosome and endoplasmic reticulum quality control pathways in Niemann-Pick type C disease","volume":"1649","author":"ML Schultz","year":"2016","journal-title":"Brain Res"},{"issue":"1","key":"pone.0243746.ref065","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1038\/s41467-018-06115-2","article-title":"Coordinate regulation of mutant NPC1 degradation by selective ER autophagy and MARCH6-dependent ERAD","volume":"9","author":"ML Schultz","year":"2018","journal-title":"Nat Commun"},{"key":"pone.0243746.ref066","doi-asserted-by":"crossref","first-page":"8212","DOI":"10.1073\/pnas.1607795113","article-title":"Structure of human Niemann-Pick C1 protein","volume":"113","author":"X Li","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0243746.ref067","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/j.cell.2016.05.022","article-title":"Structural Insights into the Niemann-Pick C1 (NPC1)-Mediated Cholesterol Transfer and Ebola Infection","volume":"165","author":"X Gong","year":"2016","journal-title":"Cell"},{"key":"pone.0243746.ref068","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1016\/j.cell.2018.10.026","article-title":"Structural Basis for Cholesterol Transport-like Activity of the Hedgehog Receptor Patched","volume":"175","author":"Y Zhang","year":"2018","journal-title":"Cell"},{"key":"pone.0243746.ref069","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/s41589-019-0370-y","article-title":"The morphogen Sonic hedgehog inhibits its receptor Patched by a pincer grasp mechanism","volume":"15","author":"AF Rudolf","year":"2019","journal-title":"Nat Chem Biol"},{"key":"pone.0243746.ref070","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/nprot.2015.043","article-title":"The FTMap family of web servers for determining and characterizing ligand-binding hot spots of proteins","volume":"10","author":"D Kozakov","year":"2015","journal-title":"Nat Protoc"},{"key":"pone.0243746.ref071","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/s41467-019-13917-5","article-title":"Structural basis for itraconazole-mediated NPC1 inhibition","volume":"11","author":"T Long","year":"2020","journal-title":"Nat Commun"},{"key":"pone.0243746.ref072","doi-asserted-by":"crossref","first-page":"176","DOI":"10.3389\/fphar.2012.00176","article-title":"Ouabain Mimics Low Temperature Rescue of F508del-CFTR in Cystic Fibrosis Epithelial Cells","volume":"3","author":"D Zhang","year":"2012","journal-title":"Front Pharmacol."},{"key":"pone.0243746.ref073","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1126\/science.1093131","article-title":"Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption","volume":"303","author":"SW Altmann","year":"2004","journal-title":"Science"},{"key":"pone.0243746.ref074","doi-asserted-by":"crossref","first-page":"8132","DOI":"10.1073\/pnas.0500269102","article-title":"The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1)","volume":"102","author":"M Garcia-Calvo","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0243746.ref075","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.7554\/eLife.57089","article-title":"Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins","volume":"9","author":"P Saha","year":"2020","journal-title":"eLife"},{"key":"pone.0243746.ref076","doi-asserted-by":"crossref","first-page":"5297","DOI":"10.1016\/j.bmc.2013.06.022","article-title":"Structure-activity relationship studies of Niemann-Pick type C1-like 1 (NPC1L1) ligands identified by screening assay monitoring pharmacological chaperone effect","volume":"21","author":"F Karaki","year":"2013","journal-title":"Bioorg Med Chem"},{"key":"pone.0243746.ref077","doi-asserted-by":"crossref","first-page":"3587","DOI":"10.1016\/j.bmc.2014.05.022","article-title":"Structure-activity relationship study of non-steroidal NPC1L1 ligands identified through cell-based assay using pharmacological chaperone effect as a readout","volume":"22","author":"F 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