{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T03:21:27Z","timestamp":1788837687686,"version":"build-2803163510"},"reference-count":156,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The lysosomal storage disorders Niemann-Pick disease Type C1 (NPC1) and Type C2 (NPC2) are rare diseases caused by mutations in the NPC1 or NPC2 gene. Both NPC1 and NPC2 are proteins responsible for the exit of cholesterol from late endosomes and lysosomes (LE\/LY). Consequently, mutations in one of the two proteins lead to the accumulation of unesterified cholesterol and glycosphingolipids in LE\/LY, displaying a disease hallmark. A total of 95% of cases are due to a deficiency of NPC1 and only 5% are caused by NPC2 deficiency. Clinical manifestations include neurological symptoms and systemic symptoms, such as hepatosplenomegaly and pulmonary manifestations, the latter being particularly pronounced in NPC2 patients. NPC1 and NPC2 are rare diseases with the described neurovisceral clinical picture, but studies with human primary patient-derived neurons and hepatocytes are hardly feasible. Obviously, induced pluripotent stem cells (iPSCs) and their derivatives are an excellent alternative for indispensable studies with these affected cell types to study the multisystemic disease NPC1. Here, we present a review focusing on studies that have used iPSCs for disease modeling and drug discovery in NPC1 and draw a comparison to commonly used NPC1 models.<\/jats:p>","DOI":"10.3390\/ijms22020710","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T20:11:31Z","timestamp":1610482291000},"page":"710","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1"],"prefix":"10.3390","volume":"22","author":[{"given":"Christin","family":"V\u00f6lkner","sequence":"first","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht Kossel\u201d, Department of Neurology, University Medical Center Rostock, 18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maik","family":"Liedtke","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht Kossel\u201d, Department of Neurology, University Medical Center Rostock, 18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7364-7791","authenticated-orcid":false,"given":"Andreas","family":"Hermann","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht Kossel\u201d, Department of Neurology, University Medical Center Rostock, 18147 Rostock, Germany"},{"name":"Center for Transdisciplinary Neurosciences Rostock (CTNR), University Medical Center Rostock, 18147 Rostock, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Rostock\/Greifswald, 18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2421-8779","authenticated-orcid":false,"given":"Moritz J.","family":"Frech","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht Kossel\u201d, Department of Neurology, University Medical Center Rostock, 18147 Rostock, Germany"},{"name":"Center for Transdisciplinary Neurosciences Rostock (CTNR), University Medical Center Rostock, 18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1750-1172-5-16","article-title":"Niemann-Pick disease type C","volume":"5","author":"Vanier","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","unstructured":"(2020, November 23). The Human Gene Mutation Database. Gene Database. Available online: http:\/\/www.hgmd.cf.ac.uk\/ac\/index.php."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ymgme.2009.06.008","article-title":"Recommendations on the diagnosis and management of Niemann-Pick disease type C","volume":"98","author":"Wraith","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_4","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":"Carstea","year":"1997","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.cell.2008.07.041","article-title":"Disease-specific induced pluripotent stem cells","volume":"134","author":"Park","year":"2008","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ymgme.2011.05.020","article-title":"Generation of induced pluripotent stem (iPS) cells derived from a murine model of Pompe disease and differentiation of Pompe-iPS cells into skeletal muscle cells","volume":"104","author":"Kawagoe","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1038\/mt.2015.106","article-title":"Arylsulfatase A Overexpressing Human iPSC-derived Neural Cells Reduce CNS Sulfatide Storage in a Mouse Model of Metachromatic Leukodystrophy","volume":"23","author":"Doerr","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1093\/hmg\/ddt596","article-title":"Human iPSC models of neuronal ceroid lipofuscinosis capture distinct effects of TPP1 and CLN3 mutations on the endocytic pathway","volume":"23","author":"Lojewski","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1182\/blood-2010-05-287607","article-title":"Hematopoietic differentiation of induced pluripotent stem cells from patients with mucopolysaccharidosis type I (Hurler syndrome)","volume":"117","author":"Tolar","year":"2011","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.5966\/sctm.2015-0373","article-title":"Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of Therapeutics for Niemann-Pick Disease Type A","volume":"5","author":"Long","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/1750-1172-8-144","article-title":"Niemann-Pick type C1 patient-specific induced pluripotent stem cells display disease specific hallmarks","volume":"8","author":"Trilck","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1080\/17460441.2019.1588882","article-title":"Animal models for Niemann-Pick type C: Implications for drug discovery & development","volume":"14","author":"Fog","year":"2019","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pallottini, V., and Pfrieger, F.W. (2020). Understanding and Treating Niemann-Pick Type C Disease: Models Matter. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21238979"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/neup.12047","article-title":"Niemann-Pick disease type C1 predominantly involving the frontotemporal region, with cortical and brainstem Lewy bodies: An autopsy case","volume":"34","author":"Chiba","year":"2014","journal-title":"Neuropathology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s10545-013-9610-6","article-title":"Human and mouse neuroinflammation markers in Niemann-Pick disease, type C1","volume":"37","author":"Cologna","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/0005-2760(80)90116-2","article-title":"A lysosomal storage disorder in mice characterized by a dual deficiency of sphingomyelinase and glucocerebrosidase","volume":"619","author":"Pentchev","year":"1980","journal-title":"Biochim. Biophys. Acta (BBA)-Lipids Lipid Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0166-4328(01)00380-1","article-title":"Cognitive deficit and development of motor impairment in a mouse model of Niemann-Pick type C disease","volume":"132","author":"Rauvala","year":"2002","journal-title":"Behav. Brain Res."},{"key":"ref_18","first-page":"140","article-title":"Lysosome lipid storage disorder in NCTR-BALB\/c mice. I. Description of the disease and genetics","volume":"108","author":"Morris","year":"1982","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4661","DOI":"10.1038\/s41598-018-21805-z","article-title":"Impact of Reduced Cerebellar EAAT Expression on Purkinje Cell Firing Pattern of NPC1-deficient Mice","volume":"8","author":"Rabenstein","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rabenstein, M., Peter, F., Joost, S., Trilck, M., Rolfs, A., and Frech, M.J. (2017). Decreased calcium flux in Niemann-Pick type C1 patient-specific iPSC-derived neurons due to higher amount of calcium-impermeable AMPA receptors. Mol. Cell. Neurosci.","DOI":"10.1016\/j.mcn.2017.06.007"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"German, D.C., Liang, C.L., Song, T., Yazdani, U., Xie, C., and Dietschy, J.M. (2002). Neurodegeneration in the Niemann-Pick C mouse: Glial involvement. Neuroscience, 109.","DOI":"10.1016\/S0306-4522(01)00517-6"},{"key":"ref_22","first-page":"1412","article-title":"Feline Niemann-Pick disease type C","volume":"144","author":"Brown","year":"1994","journal-title":"Am. J. Pathol."},{"key":"ref_23","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":"ref_24","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/oxfordjournals.jhered.a109635","article-title":"Sphingomyelinosis, a new mutation in the mouse: A model of Niemann-Pick disease in humans","volume":"73","author":"Miyawaki","year":"1982","journal-title":"J. Hered."},{"key":"ref_25","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":"Xie","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8091","DOI":"10.1523\/JNEUROSCI.4173-14.2015","article-title":"A murine Niemann-Pick C1 I1061T knock-in model recapitulates the pathological features of the most prevalent human disease allele","volume":"35","author":"Praggastis","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1093\/hmg\/ddr505","article-title":"A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations","volume":"21","author":"Maue","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/ana.10266","article-title":"Niemann-Pick type C disease: Accelerated neurofibrillary tangle formation and amyloid beta deposition associated with apolipoprotein E epsilon 4 homozygosity","volume":"52","author":"Saito","year":"2002","journal-title":"Ann. Neurol."},{"key":"ref_29","first-page":"1089","article-title":"Genetic dissection of a cell-autonomous neurodegenerative disorder: Lessons learned from mouse models of Niemann-Pick disease type C","volume":"6","author":"Lopez","year":"2013","journal-title":"Dis. Model. Mech."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3389\/fcell.2015.00002","article-title":"Induced pluripotent stem cells: Applications in regenerative medicine, disease modeling, and drug discovery","volume":"3","author":"Singh","year":"2015","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e4370","DOI":"10.7717\/peerj.4370","article-title":"Ten years of progress and promise of induced pluripotent stem cells: Historical origins, characteristics, mechanisms, limitations, and potential applications","volume":"6","author":"Omole","year":"2018","journal-title":"PeerJ"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1093\/hmg\/dds090","article-title":"Disruption and therapeutic rescue of autophagy in a human neuronal model of Niemann Pick type C1","volume":"21","author":"Ordonez","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.stemcr.2014.03.014","article-title":"Genetic and chemical correction of cholesterol accumulation and impaired autophagy in hepatic and neural cells derived from Niemann-Pick Type C patient-specific iPS cells","volume":"2","author":"Maetzel","year":"2014","journal-title":"Stem Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1177\/1087057114537378","article-title":"Niemann-Pick Disease Type C: Induced Pluripotent Stem Cell-Derived Neuronal Cells for Modeling Neural Disease and Evaluating Drug Efficacy","volume":"19","author":"Yu","year":"2014","journal-title":"J. Biomol. Screen."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5514","DOI":"10.1038\/ncomms6514","article-title":"Pathological roles of the VEGF\/SphK pathway in Niemann-Pick type C neurons","volume":"5","author":"Lee","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1002\/stem.1917","article-title":"HPGCD outperforms HPBCD as a potential treatment for Niemann-Pick disease type C during disease modeling with iPS cells","volume":"33","author":"Soga","year":"2015","journal-title":"Stem Cells"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"230","DOI":"10.5966\/sctm.2014-0127","article-title":"Rescue of an in vitro neuron phenotype identified in Niemann-Pick disease, type C1 induced pluripotent stem cell-derived neurons by modulating the WNT pathway and calcium signaling","volume":"4","author":"Efthymiou","year":"2015","journal-title":"Stem Cells Transl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2147","DOI":"10.1038\/cddis.2016.16","article-title":"Necroptosis in Niemann-Pick disease, type C1: A potential therapeutic target","volume":"7","author":"Cougnoux","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.brainres.2016.11.031","article-title":"Diversity of glycosphingolipid GM2 and cholesterol accumulation in NPC1 patient-specific iPSC-derived neurons","volume":"1657","author":"Trilck","year":"2017","journal-title":"Brain Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.dib.2017.03.042","article-title":"Dataset in support of the generation of Niemann-Pick disease Type C1 patient-specific iPS cell lines carrying the novel NPC1 mutation c.1180TC or the prevalent c.3182TC mutation-Analysis of pluripotency and neuronal differentiation","volume":"12","author":"Peter","year":"2017","journal-title":"Data Brief"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s13023-017-0697-y","article-title":"Activation of PKC triggers rescue of NPC1 patient specific iPSC derived glial cells from gliosis","volume":"12","author":"Peter","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1080\/15548627.2017.1329081","article-title":"Methyl-\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_43","doi-asserted-by":"crossref","first-page":"101737","DOI":"10.1016\/j.scr.2020.101737","article-title":"An induced pluripotent stem cell line (TRNDi001-D) from a Niemann-Pick disease type C1 (NPC1) patient carrying a homozygous p. I1061T (c. 3182TC) mutation in the NPC1 gene","volume":"44","author":"Li","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"102056","DOI":"10.1016\/j.scr.2020.102056","article-title":"Generation of an iPSC line (AKOSi006-A) from fibroblasts of a NPC1 patient, carrying the homozygous mutation p.I1061T (c.3182 T C) and a control iPSC line (AKOSi007-A) using a non-integrating Sendai virus system","volume":"49","author":"Liedtke","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"J\u00fcrs, A.V., V\u00f6lkner, C., Liedtke, M., Huth, K., Lukas, J., Hermann, A., and Frech, M.J. (2020). Oxidative Stress and Alterations in the Antioxidative Defense System in Neuronal Cells Derived from NPC1 Patient-Specific Induced Pluripotent Stem Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207667"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"102127","DOI":"10.1016\/j.scr.2020.102127","article-title":"Generation of an iPSC line (AKOSi004-A) from fibroblasts of a female adult NPC1 patient, carrying the compound heterozygous mutation p.Val1023Serfs*15\/p.Gly992Arg and of an iPSC line (AKOSi005-A) from a female adult control individual","volume":"50","author":"Liedtke","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101606","DOI":"10.1016\/j.scr.2019.101606","article-title":"Generation of the Niemann-Pick type C2 patient-derived iPSC line AKOSi001-A","volume":"41","author":"Peter","year":"2019","journal-title":"Stem Cell Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bergamin, N., Dardis, A., Beltrami, A., Cesselli, D., Rigo, S., Zampieri, S., Domenis, R., Bembi, B., and Beltrami, C.A. (2013). A human neuronal model of Niemann Pick C disease developed from stem cells isolated from patient\u2019s skin. Orphanet J. Rare Dis., 8.","DOI":"10.1186\/1750-1172-8-34"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sung, E.-A., Yu, K.-R., Shin, J.-H., Seo, Y., Kim, H.-S., Guen Koog, M., Kang, I., Kim, J.-J., Lee, B.-C., and Shin, T.-H. (2017). Generation of patient specific human neural stem cells from Niemann-Pick disease type C patient-derived fibroblasts. Oncotarget.","DOI":"10.18632\/oncotarget.19976"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Br\u00e4uer, A.U., Kuhla, A., Holzmann, C., Wree, A., and Witt, M. (2019). Current Challenges in Understanding the Cellular and Molecular Mechanisms in Niemann-Pick Disease Type C1. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184392"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/B978-0-12-386487-1.00017-1","article-title":"Analysis of cholesterol trafficking with fluorescent probes","volume":"108","author":"Maxfield","year":"2012","journal-title":"Methods Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1086\/320606","article-title":"Niemann-Pick C1 disease: Correlations between NPC1 mutations, levels of NPC1 protein, and phenotypes emphasize the functional significance of the putative sterol-sensing domain and of the cysteine-rich luminal loop","volume":"68","author":"Millat","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1086\/320599","article-title":"Niemann-Pick C variant detection by altered sphingolipid trafficking and correlation with mutations within a specific domain of NPC1","volume":"68","author":"Sun","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_54","unstructured":"Kompoliti, K., and Verhagen, L. (2010). Niemann\u2013Pick Type C. Encyclopedia of Movement Disorders, Elsevier Science."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1021\/acschemneuro.9b00248","article-title":"Cholesterol Biosynthesis and Uptake in Developing Neurons","volume":"10","author":"Anderson","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.plipres.2011.06.002","article-title":"Cholesterol metabolism in neurons and astrocytes","volume":"50","author":"Pfrieger","year":"2011","journal-title":"Prog. Lipid Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1023\/A:1022575511354","article-title":"Lipid changes in Niemann-Pick disease type C brain: Personal experience and review of the literature","volume":"24","author":"Vanier","year":"1999","journal-title":"Neurochem. Res."},{"key":"ref_58","first-page":"50","article-title":"Accumulation of GM2 Ganglioside Accumulation of GM2 in Niemann-Pick Type C Fibroblasts","volume":"20","author":"Yano","year":"1996","journal-title":"Proc. Jpn. Acad."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Taniguchi, M., Shinoda, Y., Ninomiya, H., Vanier, M.T., and Ohno, K. (2001). Sites and temporal changes of gangliosides GM1\/GM2 storage in the Niemann-Pick disease type C mouse brain. Brain Dev., 23.","DOI":"10.1016\/S0387-7604(01)00252-2"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Moreno, N., Stathakos, P., Caldwell, M.A., and Lane, J.D. (2017). Induced Pluripotent Stem Cell Neuronal Models for the Study of Autophagy Pathways in Human Neurodegenerative Disease. Cells, 6.","DOI":"10.3390\/cells6030024"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.4161\/auto.25803","article-title":"Histone post-translational modifications regulate autophagy flux and outcome","volume":"9","author":"Klionsky","year":"2013","journal-title":"Autophagy"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.4161\/15548627.2014.973338","article-title":"Defining and measuring autophagosome flux\u2014concept and reality","volume":"10","author":"Loos","year":"2014","journal-title":"Autophagy"},{"key":"ref_63","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_64","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/nature07976","article-title":"Autophagy regulates lipid metabolism","volume":"458","author":"Singh","year":"2009","journal-title":"Nature"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/jnen\/64.2.113","article-title":"Extensive involvement of autophagy in Alzheimer disease: An immuno-electron microscopy study","volume":"64","author":"Nixon","year":"2005","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_66","first-page":"25","article-title":"Apoptosis and autophagy in nigral neurons of patients with Parkinson\u2019s disease","volume":"12","author":"Anglade","year":"1997","journal-title":"Histol. Histopathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/nn.2528","article-title":"Cargo recognition failure is responsible for inefficient autophagy in Huntington\u2019s disease","volume":"13","author":"Talloczy","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"695","DOI":"10.3109\/00207454.2012.714430","article-title":"Autophagy and Its Comprehensive Impact on ALS","volume":"122","author":"Song","year":"2012","journal-title":"Int. J. Neurosci."},{"key":"ref_69","first-page":"81","article-title":"Cell-autonomous death of cerebellar purkinje neurons with autophagy in Niemann-Pick type C disease","volume":"1","author":"Ko","year":"2005","journal-title":"PLoS Genet."},{"key":"ref_70","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_71","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_72","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1093\/hmg\/ddm100","article-title":"Autophagy in Niemann-Pick C disease is dependent upon Beclin-1 and responsive to lipid trafficking defects","volume":"16","author":"Pacheco","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.nbd.2018.07.005","article-title":"Autophagy and mitophagy in ALS","volume":"122","author":"Evans","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/fnagi.2018.00004","article-title":"Autophagy and Alzheimer\u2019s Disease: From Molecular Mechanisms to Therapeutic Implications","volume":"10","author":"Uddin","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13024-017-0154-3","article-title":"Therapeutic potential of autophagy-enhancing agents in Parkinson\u2019s disease","volume":"12","author":"Moors","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in Growth, Metabolism, and Disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.freeradbiomed.2012.11.014","article-title":"Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease","volume":"62","author":"Yan","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ymgme.2010.06.018","article-title":"Oxidative stress in Niemann-Pick disease, type C","volume":"101","author":"Fu","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.mito.2019.07.003","article-title":"Mitochondrial dysfunction in neurodegenerative diseases and drug targets via apoptotic signaling","volume":"49","author":"Wu","year":"2019","journal-title":"Mitochondrion"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.lfs.2018.12.029","article-title":"Crosstalk between mitochondrial dysfunction, oxidative stress, and age related neurodegenerative disease: Etiologies and therapeutic strategies","volume":"218","author":"Elfawy","year":"2019","journal-title":"Life Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.4161\/auto.20668","article-title":"Defective mitophagy in human Niemann-Pick Type C1 neurons is due to abnormal autophagy activation","volume":"8","author":"Ordonez","year":"2012","journal-title":"Autophagy"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"11731","DOI":"10.1074\/jbc.M412898200","article-title":"Altered cholesterol metabolism in Niemann-Pick type C1 mouse brains affects mitochondrial function","volume":"280","author":"Yu","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.cmet.2006.07.006","article-title":"Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis","volume":"4","author":"Caballero","year":"2006","journal-title":"Cell Metab."},{"key":"ref_84","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_85","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez, A., Llacuna, L., Fern\u00e1ndez-Checa, J.C., and Colell, A. (2009). Mitochondrial cholesterol loading exacerbates amyloid beta peptide-induced inflammation and neurotoxicity. J. Neurosci., 29.","DOI":"10.1523\/JNEUROSCI.4909-08.2009"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.1111\/j.1582-4934.2008.00493.x","article-title":"Oxidative stress in NPC1 deficient cells: Protective effect of allopregnanolone","volume":"13","author":"Zampieri","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Cologna, S.M., Jiang, X.-S., Backlund, P.S., Cluzeau, C.V.M., Dail, M.K., Yanjanin, N.M., Siebel, S., Toth, C.L., Jun, H., and Wassif, C.A. (2012). Quantitative proteomic analysis of Niemann-Pick disease, type C1 cerebellum identifies protein biomarkers and provides pathological insight. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047845"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1442-200X.2003.01651.x","article-title":"Pathologic changes of glial cells in murine model of Niemann-Pick disease type C: Immunohistochemical, lectin-histochemical and ultrastructural observations","volume":"45","author":"Suzuki","year":"2003","journal-title":"Pediatr. Int."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Tamari, F., Chen, F.W., Li, C., Chaudhari, J., and Ioannou, Y.A. (2013). PKC activation in Niemann pick C1 cells restores subcellular cholesterol transport. PLoS.ONE., 8.","DOI":"10.1371\/journal.pone.0074169"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1042\/BC20070171","article-title":"Endosomal lipid accumulation in NPC1 leads to inhibition of PKC, hypophosphorylation of vimentin and Rab9 entrapment","volume":"101","author":"Walter","year":"2009","journal-title":"Biol. Cell"},{"key":"ref_91","unstructured":"Ioannou, Y.A., Altstiel, L., Crockford, D.R., and Kongsamut, M. (2017). Methods and Compositions for Treatment of Lipid Storage Disorders. (Application No. US000009724328B220170808), U.S. Patent."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5784","DOI":"10.1016\/S0021-9258(18)91082-3","article-title":"A genetic storage disorder in BALB\/C mice with a metabolic block in esterification of exogenous cholesterol","volume":"259","author":"Pentchev","year":"1984","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Davidson, C.D., Ali, N.F., Micsenyi, M.C., Stephney, G., Renault, S., Dobrenis, K., Ory, D.S., Vanier, M.T., and Walkley, S.U. (2009). Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006951"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/cne.10522","article-title":"Patterned Purkinje cell degeneration in mouse models of Niemann-Pick type C disease","volume":"456","author":"Sarna","year":"2003","journal-title":"J. Comp. Neurol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4661","DOI":"10.1113\/JP271195","article-title":"Cerebellar ataxias: \u0392-III spectrin\u2019s interactions suggest common pathogenic pathways","volume":"594","author":"Perkins","year":"2016","journal-title":"J. Physiol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Rabenstein, M., Murr, N., Hermann, A., Rolfs, A., and Frech, M.J. (2019). Alteration of GABAergic Input Precedes Neurodegeneration of Cerebellar Purkinje Cells of NPC1-Deficient Mice. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246288"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1093\/cercor\/bhz179","article-title":"Stimulation of mGluR1\/5 Improves Defective Internalization of AMPA Receptors in NPC1 Mutant Mouse","volume":"30","author":"Feng","year":"2020","journal-title":"Cereb. Cortex"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Feng, X., Bader, B.M., Yang, F., Segura, M., Schultz, L., Schr\u00f6der, O.H.-U., Rolfs, A., and Luo, J. (2018). Improvement of impaired electrical activity in NPC1 mutant cortical neurons upon DHPG stimulation detected by micro-electrode array. Brain Res.","DOI":"10.1016\/j.brainres.2018.05.009"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1023\/B:BOLI.0000045756.54006.17","article-title":"Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type I Gaucher disease","volume":"27","author":"Elstein","year":"2004","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"877","DOI":"10.2147\/TCRM.S5777","article-title":"New therapies in the management of Niemann-Pick type C disease: Clinical utility of miglustat","volume":"5","author":"Wraith","year":"2009","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s40265-013-0164-6","article-title":"Miglustat: A review of its use in Niemann-Pick disease type C","volume":"74","year":"2014","journal-title":"Drugs"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/S0960-9822(01)00396-7","article-title":"Critical role for glycosphingolipids in Niemann-Pick disease type C","volume":"11","author":"Zervas","year":"2001","journal-title":"Curr. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S1474-4422(07)70194-1","article-title":"Miglustat for treatment of Niemann-Pick C disease: A randomised controlled study","volume":"6","author":"Patterson","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ymgme.2009.12.006","article-title":"Miglustat in adult and juvenile patients with Niemann-Pick disease type C: Long-term data from a clinical trial","volume":"99","author":"Wraith","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1177\/0883073809344222","article-title":"Long-term miglustat therapy in children with Niemann-Pick disease type C","volume":"25","author":"Patterson","year":"2010","journal-title":"J. Child Neurol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.ymgme.2009.07.003","article-title":"Miglustat in patients with Niemann-Pick disease Type C (NP-C): A multicenter observational retrospective cohort study","volume":"98","author":"Pineda","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.ijpharm.2017.11.018","article-title":"Cyclodextrins: Structure, physicochemical properties and pharmaceutical applications","volume":"535","author":"Jansook","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.tifs.2003.09.019","article-title":"Cyclodextrins as food ingredients","volume":"15","author":"Szente","year":"2004","journal-title":"Trends Food Sci. Technol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0032-9592(03)00258-9","article-title":"Cyclodextrins and their uses: A review","volume":"39","year":"2004","journal-title":"Process Biochem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"330","DOI":"10.2174\/1568026613666131127160118","article-title":"Collaborative development of 2-hydroxypropyl-\u03b2-cyclodextrin for the treatment of Niemann-Pick type C1 disease","volume":"14","author":"Ottinger","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/nm1073","article-title":"Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone","volume":"10","author":"Griffin","year":"2004","journal-title":"Nat. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1073\/pnas.0810895106","article-title":"Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-\/- mouse","volume":"106","author":"Liu","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1194\/jlr.M000257","article-title":"Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid","volume":"51","author":"Liu","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s10545-012-9583-x","article-title":"Cyclodextrin alleviates neuronal storage of cholesterol in Niemann-Pick C disease without evidence of detectable blood-brain barrier permeability","volume":"36","author":"Pontikis","year":"2013","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.1073\/pnas.0914309107","article-title":"Endocytosis of beta-cyclodextrins is responsible for cholesterol reduction in Niemann-Pick type C mutant cells","volume":"107","author":"Rosenbaum","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1016\/S0140-6736(17)31465-4","article-title":"Intrathecal 2-hydroxypropyl-\u03b2-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: A non-randomised, open-label, phase 1\u20132 trial","volume":"390","author":"Ory","year":"2017","journal-title":"Lancet"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s40263-019-00642-2","article-title":"Long-term neuropsychological outcomes from an open-label phase 1\/2a trial of 2-hydoxypropyl-\u03b2-cyclodextrins (VTS-270) in Niemann-Pick Disease, Type C1","volume":"33","author":"Farmer","year":"2019","journal-title":"CNS Drugs"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/acn3.306","article-title":"Efficacy and ototoxicity of different cyclodextrins in Niemann-Pick C disease","volume":"3","author":"Davidson","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/S1097-2765(02)00534-8","article-title":"HDAC\u2019s at Work","volume":"9","author":"Peterson","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/ijc.11403","article-title":"Overexpression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of estrogen receptor alpha","volume":"107","author":"Kawai","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0168-9525(03)00074-X","article-title":"Transcriptional abnormalities in Huntington disease","volume":"19","author":"Sugars","year":"2003","journal-title":"Trends Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.bbrc.2007.06.116","article-title":"Defective cholesterol traffic and neuronal differentiation in neural stem cells of Niemann-Pick type C disease improved by valproic acid, a histone deacetylase inhibitor","volume":"360","author":"Kim","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_123","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":"Munkacsi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_124","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":"Pipalia","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.1176709","article-title":"Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate","volume":"325","author":"Hait","year":"2009","journal-title":"Science"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/emmm.200900036","article-title":"Treating lysosomal storage diseases with pharmacological chaperones: From concept to clinics","volume":"1","author":"Parenti","year":"2009","journal-title":"EMBO Mol. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1089\/adt.2011.0370","article-title":"Identification and characterization of pharmacological chaperones to correct enzyme deficiencies in lysosomal storage disorders","volume":"9","author":"Valenzano","year":"2011","journal-title":"ASSAY Drug Dev. Technol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1086\/302626","article-title":"Niemann-Pick C1 disease: The I1061T substitution is a frequent mutant allele in patients of Western European descent and correlates with a classic juvenile phenotype","volume":"65","author":"Millat","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_129","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":"Gelsthorpe","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Ohgane, K., Karaki, F., Dodo, K., and Hashimoto, Y. (2013). Discovery of oxysterol-derived pharmacological chaperones for NPC1: Implication for the existence of second sterol-binding site. Chem. Biol., 20.","DOI":"10.1016\/j.chembiol.2013.02.009"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Fukuda, H., Karaki, F., Dodo, K., Noguchi-Yachide, T., Ishikawa, M., Hashimoto, Y., and Ohgane, K. (2017). Phenanthridin-6-one derivatives as the first class of non-steroidal pharmacological chaperones for Niemann-Pick disease type C1 protein. Bioorganic Med. Chem. Lett., 27.","DOI":"10.1016\/j.bmcl.2017.04.062"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1126\/science.1151526","article-title":"Induced pluripotent stem cell lines derived from human somatic cells","volume":"318","author":"Yu","year":"2007","journal-title":"Science"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nrg2937","article-title":"Methods for making induced pluripotent stem cells: Reprogramming \u00e0 la carte","volume":"12","author":"Belmonte","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1038\/nbt.1503","article-title":"Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes","volume":"26","author":"Aasen","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Turksen, K., and Nagy, A. (2016). Generation of iPS Cells from Human Peripheral Blood Mononuclear Cells Using Episomal Vectors. Induced Pluripotent Stem (iPS) Cells: Methods and Protocols, Humana Press.","DOI":"10.1007\/978-1-4939-3055-5"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.omtn.2019.07.016","article-title":"Reprogramming of Urine-Derived Renal Epithelial Cells into iPSCs Using srRNA and Consecutive Differentiation into Beating Cardiomyocytes","volume":"17","author":"Steinle","year":"2019","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.neuroscience.2014.08.001","article-title":"The GABA excitatory\/inhibitory developmental sequence: A personal journey","volume":"279","year":"2014","journal-title":"Neuroscience"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.stem.2013.11.006","article-title":"Human iPSC-based modeling of late-onset disease via progerin-induced aging","volume":"13","author":"Miller","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_141","first-page":"1","article-title":"Regenerative Medicine for the Aging Brain","volume":"1","author":"Reggiani","year":"2014","journal-title":"Enliven. J. Stem Cell Res. Regen. Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4103\/1673-5374.169602","article-title":"Direct reprogramming of somatic cells into neural stem cells or neurons for neurological disorders","volume":"11","author":"Hou","year":"2016","journal-title":"Neural Regen. Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"12759","DOI":"10.1073\/pnas.0904825106","article-title":"Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-Myc expression for efficient human iPSC induction and differentiation","volume":"106","author":"Papapetrou","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1002\/stem.201","article-title":"Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells","volume":"27","author":"Zhou","year":"2009","journal-title":"Stem Cells"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"348","DOI":"10.2183\/pjab.85.348","article-title":"Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome","volume":"85","author":"Fusaki","year":"2009","journal-title":"Proc. Jpn. Acad. Ser. B"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1126\/science.1164270","article-title":"Generation of mouse induced pluripotent stem cells without viral vectors","volume":"322","author":"Okita","year":"2008","journal-title":"Science"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Si-Tayeb, K., Noto, F.K., Sepac, A., Sedlic, F., Bosnjak, Z.J., Lough, J.W., and Duncan, S.A. (2010). Generation of human induced pluripotent stem cells by simple transient transfection of plasmid DNA encoding reprogramming factors. BMC Dev. Biol., 10.","DOI":"10.1186\/1471-213X-10-81"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.stem.2010.08.012","article-title":"Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA","volume":"7","author":"Warren","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.stem.2009.05.005","article-title":"Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins","volume":"4","author":"Kim","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/nbt1418","article-title":"Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds","volume":"26","author":"Huangfu","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/nn.2638","article-title":"Ontogeny-recapitulating generation and tissue integration of ES cell-derived Purkinje cells","volume":"13","author":"Muguruma","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3389\/fbioe.2020.00070","article-title":"Maturation of Human Pluripotent Stem Cell-Derived Cerebellar Neurons in the Absence of Co-culture","volume":"8","author":"Silva","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"12301","DOI":"10.1073\/pnas.0806522105","article-title":"Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling","volume":"105","author":"Hay","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1016\/j.yexcr.2013.07.007","article-title":"Activin A and Wnt-dependent specification of human definitive endoderm cells","volume":"319","author":"Toivonen","year":"2013","journal-title":"Exp. Cell Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1007\/s00415-014-7619-x","article-title":"Phenotypic heterogeneity of Niemann-Pick disease type C in monozygotic twins","volume":"262","author":"Benussi","year":"2015","journal-title":"J. Neurol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.nbd.2014.05.033","article-title":"Bidirectional links between Alzheimer\u2019s disease and Niemann-Pick type C disease","volume":"72 Pt A","author":"Malnar","year":"2014","journal-title":"Neurobiol. 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