{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:37:36Z","timestamp":1789137456390,"version":"build-2803163510"},"reference-count":78,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["Postdoctoral Project Number 3160635 (GA)"],"award-info":[{"award-number":["Postdoctoral Project Number 3160635 (GA)"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1190334 ((SZ)"],"award-info":[{"award-number":["1190334 ((SZ)"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["11161083 (RP)"],"award-info":[{"award-number":["11161083 (RP)"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MSCA-RISE-2016- Lysomod","award":["734825  (SZ)"],"award-info":[{"award-number":["734825  (SZ)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Niemann\u2013Pick type C disease (NPCD) is a lysosomal storage disease (LSD) characterized by abnormal cholesterol accumulation in lysosomes, impaired autophagy flux, and lysosomal dysfunction. The activation of transcription factor EB (TFEB), a master lysosomal function regulator, reduces the accumulation of lysosomal substrates in LSDs where the degradative capacity of the cells is compromised. Genistein can pass the blood\u2013brain barrier and activate TFEB. Hence, we investigated the effect of TFEB activation by genistein toward correcting the NPC phenotype. We show that genistein promotes TFEB translocation to the nucleus in HeLa TFEB-GFP, Huh7, and SHSY-5Y cells treated with U18666A and NPC1 patient fibroblasts. Genistein treatment improved lysosomal protein expression and autophagic flux, decreasing p62 levels and increasing those of the LC3-II in NPC1 patient fibroblasts. Genistein induced an increase in \u03b2-hexosaminidase activity in the culture media of NPC1 patient fibroblasts, suggesting an increase in lysosomal exocytosis, which correlated with a decrease in cholesterol accumulation after filipin staining, including cells treated with U18666A and NPC1 patient fibroblasts. These results support that genistein-mediated TFEB activation corrects pathological phenotypes in NPC models and substantiates the need for further studies on this isoflavonoid as a potential therapeutic agent to treat NPCD and other LSDs with neurological compromise.<\/jats:p>","DOI":"10.3390\/ijms22084220","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T11:21:38Z","timestamp":1618831298000},"page":"4220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Genistein Activates Transcription Factor EB and Corrects Niemann\u2013Pick C Phenotype"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5253-4288","authenticated-orcid":false,"given":"Graciela","family":"Arg\u00fcello","sequence":"first","affiliation":[{"name":"Departament of Gastroenterology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 3580000, Chile"},{"name":"School of Health Sciences, Universidad Cat\u00f3lica del Maule, Talca 3466706, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Balboa","sequence":"additional","affiliation":[{"name":"Departament of Gastroenterology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 3580000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo J.","family":"Tapia","sequence":"additional","affiliation":[{"name":"Departament of Gastroenterology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 3580000, Chile"},{"name":"Center for Cell Biology and Biomedicine (CEBICEM), School of Science and Medicine, Universidad San Sebasti\u00e1n, Santiago 7510235, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Castro","sequence":"additional","affiliation":[{"name":"Departament of Gastroenterology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 3580000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Ya\u00f1ez","sequence":"additional","affiliation":[{"name":"Departament of Gastroenterology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 3580000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8505-4088","authenticated-orcid":false,"given":"Pamela","family":"Mattar","sequence":"additional","affiliation":[{"name":"Departament of Physiology, School of Biological Science, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 3580000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Pulgar","sequence":"additional","affiliation":[{"name":"Laboratory of Genomics and Genetics of Biological Interactions, Instituto de Nutrici\u00f3n y Tecnolog\u00eda de los Alimentos (INTA), Universidad de Chile, Santiago 7830490, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Zanlungo","sequence":"additional","affiliation":[{"name":"Departament of Gastroenterology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 3580000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,19]]},"reference":[{"key":"ref_1","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":"Winkler","year":"2019","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"962","DOI":"10.2353\/ajpath.2007.070052","article-title":"Cholesterol accumulation is associated with lysosomal dysfunction and autophagic stress in NPC1 -\/- mouse brain","volume":"171","author":"Liao","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_3","first-page":"205713","article-title":"Oxidative Stress: A Pathogenic Mechanism for Niemann-Pick Type C Disease","volume":"2012","author":"Balboa","year":"2012","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.nbd.2013.12.018","article-title":"The autophagic defect in Niemann\u2013Pick disease type C neurons differs from somatic cells and reduces neuronal viability","volume":"64","author":"Meske","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"982","DOI":"10.3389\/fphys.2017.00982","article-title":"Lysosomal and Mitochondrial Liaisons in Niemann-Pick Disease","volume":"8","author":"Torres","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/hep.20868","article-title":"Cholesterol accumulation and liver cell death in mice with Niemann-Pick type C disease","volume":"42","author":"Beltroy","year":"2005","journal-title":"Hepatology"},{"key":"ref_7","first-page":"3","article-title":"Niemann\u2013Pick C research from mouse to gene","volume":"1685","author":"Pentchev","year":"2004","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13023-018-0785-7","article-title":"Consensus clinical management guidelines for Niemann-Pick disease type C","volume":"13","author":"Geberhiwot","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41580-019-0185-4","article-title":"Lysosomes as dynamic regulators of cell and organismal homeostasis","volume":"21","author":"Ballabio","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"719","DOI":"10.4161\/auto.19469","article-title":"Autophagy in lysosomal storage disorders","volume":"8","author":"Lieberman","year":"2012","journal-title":"Autophagy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"487","DOI":"10.4161\/auto.4586","article-title":"Lipid Trafficking Defects Increase Beclin-1 and Activate Autophagy in Niemann-Pick Type C Disease","volume":"3","author":"Pacheco","year":"2007","journal-title":"Autophagy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e26","DOI":"10.1017\/S146239940800080X","article-title":"The pathogenesis of Niemann\u2013Pick type C disease: A role for autophagy?","volume":"10","author":"Pacheco","year":"2008","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.jocn.2008.09.020","article-title":"Association of autophagy with cholesterol-accumulated compartments in Nie-mann-Pick disease type C cells","volume":"16","author":"Ishibashi","year":"2009","journal-title":"J. Clin. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4876","DOI":"10.1093\/hmg\/dds324","article-title":"Impaired proteolysis underlies autophagic dysfunction in Niemann\u2013Pick type C disease","volume":"21","author":"Elrick","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sobo, K., Le Blanc, I., Luyet, P.-P., Fivaz, M., Ferguson, C., Parton, R.G., Gruenberg, J., and Van Der Goot, F.G. (2007). Late Endosomal Cholesterol Accumulation Leads to Impaired Intra-Endosomal Trafficking. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000851"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1038\/emboj.2010.237","article-title":"Lysosomal fusion and SNARE function are impaired by cholesterol accumulation in lysosomal storage disorders","volume":"29","author":"Fraldi","year":"2010","journal-title":"EMBO J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1096\/fj.09-144519","article-title":"Altered lipid content inhibits autophagic vesicular fusion","volume":"24","author":"Koga","year":"2010","journal-title":"FASEB J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.celrep.2013.10.042","article-title":"Impaired Autophagy in the Lipid-Storage Disorder Niemann-Pick Type C1 Disease","volume":"5","author":"Sarkar","year":"2013","journal-title":"Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s10048-019-00600-6","article-title":"Changes in global gene expression indicate disordered autophagy, apoptosis and inflammatory processes and downregulation of cytoskeletal signalling and neuronal development in patients with Niemann-Pick C disease","volume":"21","author":"Fogtman","year":"2020","journal-title":"Neurogenetics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1056\/NEJMra1205406","article-title":"Autophagy in Human Health and Disease","volume":"368","author":"Choi","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1126\/science.1174447","article-title":"A Gene Network Regulating Lysosomal Biogenesis and Function","volume":"325","author":"Sardiello","year":"2009","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3852","DOI":"10.1093\/hmg\/ddr306","article-title":"Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways","volume":"20","author":"Palmieri","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.4161\/cc.8.24.10263","article-title":"Lysosomal enhancement: A CLEAR answer to cellular degradative needs","volume":"8","author":"Sardiello","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.devcel.2011.07.016","article-title":"Transcriptional activation of lysosomal exocytosis pro-motes cellular clearance","volume":"21","author":"Medina","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/nyas.13131","article-title":"Transcription factor EB: From master coordinator of lysosomal pathways to candidate therapeutic target in degenerative storage diseases","volume":"1371","author":"Sardiello","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.4161\/auto.7.11.17166","article-title":"TFEB regulates autophagy: An integrated coordination of cellular degradation and recycling pro-cesses","volume":"7","author":"Settembre","year":"2011","journal-title":"Autophagy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/ncb2718","article-title":"TFEB controls cellular lipid metabolism through a star-vation-induced autoregulatory loop","volume":"15","author":"Settembre","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Buratta, S., Tancini, B., Sagini, K., Delo, F., Chiaradia, E., Urbanelli, L., and Emiliani, C. (2020). Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072576"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Xu, Y., Du, S., Marsh, J.A., Horie, K., Sato, C., Ballabio, A., Karch, C.M., Holtzman, D.M., and Zheng, H. (2020). TFEB regulates lysosomal exocytosis of tau and its loss of function exacerbates tau pathology and spreading. Mol. Psychiatry, 1\u201315.","DOI":"10.1038\/s41380-020-0738-0"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1194\/jlr.R046896","article-title":"Lysosomal exocytosis and lipid storage disorders","volume":"55","author":"Samie","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"jcs221739","DOI":"10.1242\/jcs.221739","article-title":"Lysosomal storage disorders\u2014Challenges, concepts and avenues for therapy: Beyond rare diseases","volume":"132","author":"Marques","year":"2019","journal-title":"J. Cell Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5760","DOI":"10.1523\/JNEUROSCI.3085-18.2019","article-title":"Increased Lysosomal Exocytosis Induced by Lysosomal Ca2+ Channel Agonists Protects Human Dopaminergic Neurons from \u03b1-Synuclein Toxicity","volume":"39","author":"Tsunemi","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/emmm.201202176","article-title":"Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease","volume":"5","author":"Spampanato","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.4161\/auto.24920","article-title":"What else is in store for autophagy? Ex-ocytosis of autolysosomes as a mechanism of TFEB-mediated cellular clearance in Pompe disease","volume":"9","author":"Feeney","year":"2013","journal-title":"Autophagy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/emmm.201202046","article-title":"Gene transfer of master autophagy regulator TFEB results in clearance of toxic protein and correction of hepatic disease in alpha-1-anti-trypsin deficiency","volume":"5","author":"Pastore","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"73","DOI":"10.15252\/emmm.201505966","article-title":"The awesome lysosome","volume":"8","author":"Ballabio","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.15252\/emmm.201303671","article-title":"Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB","volume":"6","author":"Li","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12137","DOI":"10.1523\/JNEUROSCI.0705-15.2015","article-title":"Neuronal-Targeted TFEB Accelerates Lysosomal Degradation of APP, Reducing A Generation and Amyloid Plaque Pathogenesis","volume":"35","author":"Xiao","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"15793","DOI":"10.1038\/ncomms15793","article-title":"Corrigendum: mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neuro-degenerative storage diseases","volume":"8","author":"Palmieri","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"142ra97","DOI":"10.1126\/scitranslmed.3003799","article-title":"PGC-1\u03b1 rescues Huntington\u2019s disease proteotoxicity by preventing oxidative stress and promoting TFEB function","volume":"4","author":"Tsunemi","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"101691","DOI":"10.1016\/j.isci.2020.101691","article-title":"c-Abl Inhibition Activates TFEB and Promotes Cellular Clearance in a Lysosomal Disorder","volume":"23","author":"Contreras","year":"2020","journal-title":"iScience"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.chroma.2004.10.048","article-title":"Concurrent measurement of unbound genistein in the blood, brain and bile of anesthetized rats using microdialysis and its pharmacokinetic application","volume":"1073","author":"Tsai","year":"2005","journal-title":"J. Chromatogr. A"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1111\/j.1476-5381.2009.00565.x","article-title":"Genistein reduces glycosaminoglycan levels in a mouse model of muco-polysaccharidosis type II","volume":"159","author":"Friso","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.ymgme.2013.06.012","article-title":"High dose genistein aglycone therapy is safe in patients with muco-polysaccharidoses involving the central nervous system","volume":"109","author":"Kim","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_45","first-page":"21","article-title":"The use of elevated doses of genistein-rich soy extract in the gene expression-targeted isoflavone therapy for Sanfilippo disease patients","volume":"5","author":"Narajczyk","year":"2012","journal-title":"JIMD Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9378","DOI":"10.1038\/srep09378","article-title":"Modulation of expression of genes involved in glycosaminoglycan metabolism and lysosome biogenesis by flavonoids","volume":"5","author":"Moskot","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s12017-018-8482-1","article-title":"Correction of Huntington\u2019s Disease Phenotype by Genistein-Induced Autophagy in the Cellular Model","volume":"20","author":"Pierzynowska","year":"2018","journal-title":"NeuroMolecular Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.kint.2015.12.045","article-title":"Activation of the transcription factor EB rescues lysosomal abnormalities in cystinotic kidney cells","volume":"89","author":"Rega","year":"2016","journal-title":"Kidney Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e12177","DOI":"10.7554\/eLife.12177","article-title":"Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection","volume":"4","author":"Lu","year":"2015","journal-title":"eLife"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3389\/fcell.2019.00114","article-title":"Transcriptional Regulation of Autophagy: Mechanisms and Diseases","volume":"7","author":"Cinque","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"40797","DOI":"10.1038\/srep40797","article-title":"TFEB-mediated increase in peripheral lysosomes regulates store-operated calcium entry","volume":"7","author":"Sbano","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1093\/emboj\/19.21.5720","article-title":"LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing","volume":"19","author":"Kabeya","year":"2000","journal-title":"EMBO J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.phrs.2012.07.004","article-title":"p62\/SQSTM1\/A170: Physiology and pathology","volume":"66","author":"Komatsu","year":"2012","journal-title":"Pharmacol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ymeth.2014.11.021","article-title":"LC3- and p62-based biochemical methods for the analysis of autophagy progression in mammalian cells","volume":"75","author":"Jiang","year":"2015","journal-title":"Methods"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.bbadis.2011.11.009","article-title":"Lysosomal vitamin E accumulation in Niemann\u2013Pick type C disease","volume":"1822","author":"Klein","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17054","DOI":"10.1074\/jbc.M114.555300","article-title":"The Phytoestrogen Genistein Modulates Lysosomal Metabolism and Transcription Factor EB (TFEB) Activation","volume":"289","author":"Moskot","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1242\/jcs.146365","article-title":"TFEB at a glance","volume":"129","author":"Napolitano","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_58","first-page":"135","article-title":"Controversies on the potential therapeutic use of rapamycin for treating a lysosomal cholesterol storage disease","volume":"15","author":"Klein","year":"2018","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1194\/jlr.M013789","article-title":"Quantitative role of LAL, NPC2, and NPC1 in lysosomal cholesterol processing defined by genetic and pharmacological manipulations","volume":"52","author":"Ramirez","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1080\/15548627.2017.1329081","article-title":"Me-thyl-\u03b2-cyclodextrin restores impaired autophagy flux in Niemann-Pick C1-deficient cells through activation of AMPK","volume":"13","author":"Dai","year":"2017","journal-title":"Autophagy"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s13041-019-0504-x","article-title":"Autophagic and endo-lysosomal dysfunction in neurodegenerative disease","volume":"12","author":"Malik","year":"2019","journal-title":"Mol. Brain"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.2174\/13816128113199990320","article-title":"Curcumin and Genistein: The Combined Effects on Disease-associated CFTR Mutants and their Clinical Implications","volume":"19","author":"Yu","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"540726","DOI":"10.3389\/fcell.2020.540726","article-title":"Proteasome Composition and Activity Changes in Cultured Fibroblasts Derived from Mucopolysaccharidoses Patients and Their Modula-tion by Genistein","volume":"8","author":"Pierzynowska","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1159\/000107531","article-title":"Cholesterol Depletion and Genistein as Tools to Promote F508delCFTR Retention at the Plasma Membrane","volume":"20","author":"Lim","year":"2007","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3874","DOI":"10.1016\/j.bmcl.2008.06.051","article-title":"Activation of CFTR by UCCF-029 and genistein","volume":"18","author":"Springsteel","year":"2008","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1038\/sj.bjp.0707663","article-title":"Prolonged treatment of cells with genistein modulates the expression and function of the cystic fibrosis transmembrane conductance regulator","volume":"153","author":"Schmidt","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.curtheres.2008.04.002","article-title":"Genistin-rich soy isoflavone extract in substrate reduction therapy for Sanfilippo syndrome: An open-label, pilot study in 10 pediatric patients","volume":"69","author":"Piotrowska","year":"2008","journal-title":"Curr. Ther. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s10545-014-9703-x","article-title":"Genistein increases glycosaminoglycan levels in mu-copolysaccharidosis type I cell models","volume":"37","author":"Kingma","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/8904_2015_432","article-title":"Adverse Effects of Genistein in a Mucopolysaccharidosis Type I Mouse Model","volume":"23","author":"Kingma","year":"2015","journal-title":"JIMD Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s10545-011-9342-4","article-title":"Genistein supplementation in patients affected by Sanfilippo disease","volume":"34","author":"Delgadillo","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/ana.22643","article-title":"Genistein in Sanfilippo disease: A randomized controlled crossover trial","volume":"71","author":"Valstar","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.tins.2016.02.002","article-title":"The Autophagy\u2013Lysosomal Pathway in Neurodegeneration: A TFEB Perspective","volume":"39","author":"Xu","year":"2016","journal-title":"Trends Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1194\/jlr.M072140","article-title":"Histone deacetylase inhibitors correct the cholesterol storage defect in most Niemann-Pick C1 mutant cells","volume":"58","author":"Pipalia","year":"2017","journal-title":"J. Lipid Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1126\/science.1204592","article-title":"TFEB Links Autophagy to Lysosomal Biogenesis","volume":"332","author":"Settembre","year":"2011","journal-title":"Science"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1104\/pp.105.076232","article-title":"Zinc-Dependent Global Transcriptional Control, Transcriptional Deregulation, and Higher Gene Copy Number for Genes in Metal Homeostasis of the Hyperaccumulator Arabidopsis halleri","volume":"142","author":"Talke","year":"2006","journal-title":"Plant Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"39349","DOI":"10.1074\/jbc.M112.357707","article-title":"\u03b4-Tocopherol Reduces Lipid Accumulation in Niemann-Pick Type C1 and Wolman Cholesterol Storage Disorders*","volume":"287","author":"Xu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/S0304-3940(02)01423-4","article-title":"Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data","volume":"339","author":"Ramakersab","year":"2003","journal-title":"Neurosci. Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/4220\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:49:46Z","timestamp":1760161786000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/4220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,19]]},"references-count":78,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22084220"],"URL":"https:\/\/doi.org\/10.3390\/ijms22084220","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,19]]}}}