{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:31:43Z","timestamp":1785223903312,"version":"3.55.0"},"reference-count":75,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T00:00:00Z","timestamp":1491436800000},"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>Niemann\u2013Pick disease type C1 (NPC1) is a fatal neurovisceral lysosomal lipid storage disorder. The mutation of the NPC1 protein affects the homeostasis and transport of cholesterol and glycosphingolipids from late endosomes\/lysosomes to the endoplasmic reticulum resulting in progressive neurodegeneration. Since olfactory impairment is one of the earliest symptoms in many neurodegenerative disorders, we focused on alterations of the olfactory epithelium in an NPC1 mouse model. Previous findings revealed severe morphological and immunohistochemical alterations in the olfactory system of NPC1\u2212\/\u2212 mutant mice compared with healthy controls (NPC1+\/+). Based on immunohistochemical evaluation of the olfactory epithelium, we analyzed the impact of neurodegeneration in the olfactory epithelium of NPC1\u2212\/\u2212 mice and observed considerable loss of mature olfactory receptor neurons as well as an increased number of proliferating and apoptotic cells. Additionally, after administration of two different therapy approaches using either a combination of miglustat, 2-hydroxypropyl-\u03b2-cyclodextrin (HP\u03b2CD) and allopregnanolone or a monotherapy with HP\u03b2CD, we recorded a remarkable reduction of morphological damages in NPC1\u2212\/\u2212 mice and an up to four-fold increase of proliferating cells within the olfactory epithelium. Numbers of mature olfactory receptor neurons doubled after both therapy approaches. Interestingly, we also observed therapy-induced alterations in treated NPC1+\/+ controls. Thus, olfactory testing may provide useful information to monitor pharmacologic treatment approaches in human NPC1.<\/jats:p>","DOI":"10.3390\/ijms18040777","type":"journal-article","created":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T09:57:30Z","timestamp":1491472650000},"page":"777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Increased Regenerative Capacity of the Olfactory Epithelium in Niemann\u2013Pick Disease Type C1"],"prefix":"10.3390","volume":"18","author":[{"given":"Anja","family":"Meyer","sequence":"first","affiliation":[{"name":"Institute of Anatomy, University of Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wree","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7977-9093","authenticated-orcid":false,"given":"Carsten","family":"Holzmann","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Rolfs","sequence":"additional","affiliation":[{"name":"Albrecht-Kossel Institute for Neuroregeneration, Rostock University Medical Center, 18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4538-877X","authenticated-orcid":false,"given":"Martin","family":"Witt","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/ana.21291","article-title":"Association of olfactory dysfunction with risk for future Parkinson\u2019s disease","volume":"63","author":"Ross","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1093\/qjmed\/92.8.473","article-title":"Is Parkinson\u2019s disease a primary olfactory disorder?","volume":"92","author":"Hawkes","year":"1999","journal-title":"QJM"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1212\/WNL.38.8.1237","article-title":"Olfactory dysfunction in Parkinsonism: A general deficit unrelated to neurologic signs, disease stage, or disease duration","volume":"38","author":"Doty","year":"1988","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1001\/archneur.55.1.84","article-title":"Olfaction in neurodegenerative disease: A meta-analysis of olfactory functioning in Alzheimer\u2019s and Parkinson\u2019s diseases","volume":"55","author":"Mesholam","year":"1998","journal-title":"Arch. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.neurobiolaging.2006.11.014","article-title":"Olfaction in patients with mild cognitive impairment and Alzheimer\u2019s disease","volume":"29","author":"Djordjevic","year":"2008","journal-title":"Neurobiol. Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1080\/01688638708405208","article-title":"Olfactory recognition: Differential impairments in early and late Huntington\u2019s and Alzheimer\u2019s diseases","volume":"9","author":"Moberg","year":"1987","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/chemse\/bjt072","article-title":"Olfactory disorders and quality of life\u2014An updated review","volume":"39","author":"Croy","year":"2014","journal-title":"Chem. Sens."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1177\/0898264309353066","article-title":"Prevalence and neurodegenerative or other associations with olfactory impairment in an older community","volume":"22","author":"Karpa","year":"2010","journal-title":"J. Aging Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0736-5748(96)00046-9","article-title":"The aging olfactory epithelium: Neurogenesis, response to damage, and odorant-induced activity","volume":"14","author":"Loo","year":"1996","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF01206454","article-title":"Neurogenesis and neuron regeneration in the olfactory system of mammals. I. Morphological aspects of differentiation and structural organization of the olfactory sensory neurons","volume":"8","author":"Graziadei","year":"1979","journal-title":"J. Neurocytol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1006\/exnr.1993.1201","article-title":"The dynamics of cell death in the olfactory epithelium","volume":"124","author":"Carr","year":"1993","journal-title":"Exp. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Doty, R.L. (2015). Neurogenesis in the adult olfactory epithelium. Handbook of Olfaction and Gustation, John Wiley & Sons. [3rd ed.].","DOI":"10.1002\/9781118971758"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1002\/cne.24105","article-title":"Stem and progenitor cells of the mammalian olfactory epithelium: Taking poietic license","volume":"525","author":"Schwob","year":"2017","journal-title":"J. Comp. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hovakimyan, M., Meyer, A., Lukas, J., Luo, J., Gudziol, V., Hummel, T., Rolfs, A., Wree, A., and Witt, M. (2013). Olfactory deficits in Niemann-Pick Pick type C1 (NPC1) disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082216"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1016\/j.bbadis.2014.08.005","article-title":"Excessive microglial activation aggravates olfactory dysfunction by impeding the survival of newborn neurons in the olfactory bulb of Niemann-Pick disease type C1 mice","volume":"1842","author":"Seo","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1042\/BJ20050236","article-title":"NPC1 late endosomes contain elevated levels of non-esterified (\u2019free\u2019) fatty acids and an abnormally glycosylated form of the NPC2 protein","volume":"390","author":"Chen","year":"2005","journal-title":"Biochem. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9627","DOI":"10.1074\/jbc.274.14.9627","article-title":"The Niemann-Pick C1 protein resides in a vesicular compartment linked to retrograde transport of multiple lysosomal cargo","volume":"274","author":"Neufeld","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_18","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\u2212\/\u2212 mouse brain","volume":"171","author":"Liao","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1016\/S0021-9258(18)69086-6","article-title":"Type C Niemann-Pick disease. Lysosomal accumulation and defective intracellular mobilization of low density lipoprotein cholesterol","volume":"263","author":"Sokol","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"26167","DOI":"10.1074\/jbc.M311591200","article-title":"Accumulation of glycosphingolipids in Niemann-Pick C disease disrupts endosomal transport","volume":"279","author":"Veldman","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/jnr.23509","article-title":"Reduced cerebellar neurodegeneration after combined therapy with cyclodextrin\/allopregnanolone and miglustat in NPC1: A mouse model of Niemann-Pick type C1 disease","volume":"93","author":"Maass","year":"2015","journal-title":"J. Neurosci. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/BF00690966","article-title":"Niemann-Pick disease type C. Study on the nature of the cerebral storage process","volume":"66","author":"Elleder","year":"1985","journal-title":"Acta Neuropathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1097\/00005072-198805000-00008","article-title":"Cerebellar involvement in murine sphingomyelinosis: A new model of Niemann-Pick disease","volume":"47","author":"Tanaka","year":"1988","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/BF00227765","article-title":"Cerebellar degeneration in the Niemann-Pick type C mouse","volume":"85","author":"Higashi","year":"1993","journal-title":"Acta Neuropathol."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/cne.1149","article-title":"Selective neurodegeneration, without neurofibrillary tangles, in a mouse model of Niemann-Pick C disease","volume":"433","author":"German","year":"2001","journal-title":"J. Comp. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S0387-7604(01)00209-1","article-title":"Progressive neuronal loss in the ventral posterior lateral and medial nuclei of thalamus in Niemann-Pick disease type C mouse brain","volume":"23","author":"Yamada","year":"2001","journal-title":"Brain Dev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/brain\/118.1.119","article-title":"Neurofibrillary tangles in Niemann-Pick disease type C","volume":"118","author":"Love","year":"1995","journal-title":"Brain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s11011-011-9263-9","article-title":"Decreased expression of myelin gene regulatory factor in Niemann-Pick type C 1 mouse","volume":"26","author":"Yan","year":"2011","journal-title":"Metab. Brain Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/(SICI)1097-4547(19970801)49:3<389::AID-JNR14>3.0.CO;2-V","article-title":"Cholesterol reutilization during myelination of regenerating pns axons is impaired in Niemann-Pick disease type C mice","volume":"49","author":"Goodrum","year":"1997","journal-title":"J. Neurosci. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yu, T., and Lieberman, A.P. (2013). NPC1 acting in neurons and glia is essential for the formation and maintenance of cns myelin. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003462"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0306-4522(01)00517-6","article-title":"Neurodegeneration in the Niemann-Pick C mouse: Glial involvement","volume":"109","author":"German","year":"2002","journal-title":"Neuroscience"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1651-2227.2008.00656.x","article-title":"Substrate reduction therapy","volume":"97","author":"Platt","year":"2008","journal-title":"Acta Paediatr."},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2217\/clp.12.31","article-title":"Therapeutic potential of cyclodextrins in the treatment of Niemann\u2013Pick type C disease","volume":"7","author":"Liu","year":"2012","journal-title":"Clin. Lipidol."},{"key":"ref_36","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\u2212\/\u2212 mouse","volume":"106","author":"Liu","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","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_38","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1194\/jlr.M028241","article-title":"Cyclodextrin mediates rapid changes in lipid balance in NPC1\u2212\/\u2212 mice without carrying cholesterol through the bloodstream","volume":"53","author":"Taylor","year":"2012","journal-title":"J. Lipid Res."},{"key":"ref_39","unstructured":"Vtesse. Inc. (2017, March 06). Study of 2-Hydroxypropyl-Beta-Cyclodextrin (vts-270) to Treat Niemann-Pick Type C1 (NPC1) Disease. Clinicaltrials, Available online: https:\/\/clinicaltrials.Gov\/ct2\/show\/study\/nct02534844."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9404","DOI":"10.1523\/JNEUROSCI.1317-11.2011","article-title":"Unesterified cholesterol accumulation in late endosomes\/lysosomes causes neurodegeneration and is prevented by driving cholesterol export from this compartment","volume":"31","author":"Aqul","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/S0022-2836(02)00282-6","article-title":"Olfactory marker protein (OMP) exhibits a beta-clam fold in solution: Implications for target peptide interaction and olfactory signal transduction","volume":"319","author":"Baldisseri","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.1365-3083.1982.tb03764.x","article-title":"Olfactory marker protein (OMP)","volume":"9","author":"Margolis","year":"1982","journal-title":"Scand. J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1002\/ana.21910","article-title":"Olfactory epithelium amyloid-beta and paired helical filament-tau pathology in Alzheimer disease","volume":"67","author":"Arnold","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_44","first-page":"265","article-title":"Olfactory tau pathology in Alzheimer disease and mild cognitive impairment","volume":"25","author":"Attems","year":"2006","journal-title":"Clin. Neuropathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1212\/WNL.0000000000001132","article-title":"Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community","volume":"84","author":"Devanand","year":"2015","journal-title":"Neurology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/ana.1049","article-title":"Subclinical dopaminergic dysfunction in asymptomatic Parkinson\u2019s disease patients\u2019 relatives with a decreased sense of smell","volume":"50","author":"Berendse","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jns.2009.08.026","article-title":"Immunohistochemical, volumetric, and functional neuroimaging studies in patients with idiopathic Parkinson\u2019s disease","volume":"289","author":"Hummel","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1002\/(SICI)1096-9861(19981102)400:4<469::AID-CNE3>3.0.CO;2-8","article-title":"Adult olfactory epithelium contains multipotent progenitors that give rise to neurons and non-neural cells","volume":"400","author":"Huard","year":"1998","journal-title":"J. Comp. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/chemse\/bju062","article-title":"Stereological estimation of olfactory receptor neurons in rats","volume":"40","author":"Kawagishi","year":"2015","journal-title":"Chem. Sens."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.1093\/hmg\/dds193","article-title":"Microarray expression analysis and identification of serum biomarkers for Niemann-Pick disease, type C1","volume":"21","author":"Cluzeau","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"10998","DOI":"10.1073\/pnas.88.24.10998","article-title":"Lysosomal hydrolases of different classes are abnormally distributed in brains of patients with Alzheimer disease","volume":"88","author":"Cataldo","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/00005072-199903000-00007","article-title":"Quantitative decrease in synaptophysin message expression and increase in cathepsin D message expression in Alzheimer disease neurons containing neurofibrillary tangles","volume":"58","author":"Callahan","year":"1999","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/1531-8249(200007)48:1<77::AID-ANA12>3.0.CO;2-A","article-title":"Expression profile of transcripts in Alzheimer\u2019s disease tangle-bearing CA1 neurons","volume":"48","author":"Ginsberg","year":"2000","journal-title":"Ann. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1093\/hmg\/ddq273","article-title":"Altered expression and distribution of cathepsins in neuronopathic forms of Gaucher disease and in other sphingolipidoses","volume":"19","author":"Vitner","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1074\/jbc.M112.412460","article-title":"Role of Cathepsin D in U18666A-induced neuronal cell death: Potential implication in Niemann-Pick type C disease pathogenesis","volume":"288","author":"Amritraj","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.neuroscience.2013.08.001","article-title":"Combined therapy with cyclodextrin\/allopregnanolone and miglustat improves motor but not cognitive functions in Niemann-Pick type C1 mice","volume":"252","author":"Hovakimyan","year":"2013","journal-title":"Neuroscience"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hovakimyan, M., Petersen, J., Maass, F., Reichard, M., Witt, M., Lukas, J., Stachs, O., Guthoff, R., Rolfs, A., and Wree, A. (2011). Corneal alterations during combined therapy with cyclodextrin\/allopregnanolone and miglustat in a knock-out mouse model of npc1 disease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028418"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1248\/bpb.b14-00726","article-title":"Efficacy of 2-hydroxypropyl-beta-cyclodextrin in Niemann-Pick disease type C model mice and its pharmacokinetic analysis in a patient with the disease","volume":"38","author":"Tanaka","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ymgme.2015.07.001","article-title":"Intrathecal 2-hydroxypropyl-beta-cyclodextrin in a single patient with Niemann-Pick C1","volume":"116","author":"Maarup","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ymgme.2012.11.005","article-title":"Effects of cyclodextrin in two patients with Niemann-Pick type C disease","volume":"108","author":"Matsuo","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Crumling, M.A., Liu, L., Thomas, P.V., Benson, J., Kanicki, A., Kabara, L., Halsey, K., Dolan, D., and Duncan, R.K. (2012). Hearing loss and hair cell death in mice given the cholesterol-chelating agent hydroxypropyl-beta-cyclodextrin. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0053280"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1203\/PDR.0b013e3181df4623","article-title":"2-hydroxypropyl-beta-cyclodextrin raises hearing threshold in normal cats and in cats with Niemann-Pick type C disease","volume":"68","author":"Ward","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"276ra226","DOI":"10.1126\/scitranslmed.3010101","article-title":"Intracisternal cyclodextrin prevents cerebellar dysfunction and purkinje cell death in feline Niemann-Pick type C1 disease","volume":"7","author":"Vite","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Megias-Vericat, J.E., Garcia-Robles, A., Company-Albir, M.J., Fernandez-Megia, M.J., Perez-Miralles, F.C., Lopez-Briz, E., Casanova, B., and Poveda, J.L. (2017). Early experience with compassionate use of 2 hydroxypropyl-beta-cyclodextrin for Niemann-Pick type C disease: Review of initial published cases. Neurol. Sci.","DOI":"10.1007\/s10072-017-2833-9"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/0166-2236(90)90017-5","article-title":"Olfactory neurogenesis: Genetic or environmental controls?","volume":"13","author":"Farbman","year":"1990","journal-title":"Trends Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/ar.1092100213","article-title":"An autoradiographic study of the mouse olfactory epithelium: Evidence for long-lived receptors","volume":"210","author":"Hinds","year":"1984","journal-title":"Anat. Rec."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S0896-6273(03)00601-9","article-title":"Diversity in the mechanisms of neuronal cell death","volume":"40","author":"Yuan","year":"2003","journal-title":"Neuron"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Schlegel, V., Thieme, M., Holzmann, C., Witt, M., Grittner, U., Rolfs, A., and Wree, A. (2016). Pharmacologic treatment assigned for Niemann Pick type C1 disease partly changes behavioral traits in wild-type mice. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111866"},{"key":"ref_69","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_70","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/jbm.a.31195","article-title":"Influence of cyclodextrins on the proliferation of HaCaT keratinocytes in vitro","volume":"83","author":"Hipler","year":"2007","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Yokoo, M., Kubota, Y., Motoyama, K., Higashi, T., Taniyoshi, M., Tokumaru, H., Nishiyama, R., Tabe, Y., Mochinaga, S., and Sato, A. (2015). 2-hydroxypropyl-beta-cyclodextrin acts as a novel anticancer agent. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141946"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1523\/JNEUROSCI.4520-04.2005","article-title":"The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates cell-cycle gene and protein expression","volume":"25","author":"Wang","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_73","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_74","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/BF00268909","article-title":"Improved methodology for detecting bromodeoxyuridine in cultured cells and tissue sections by immunocytochemistry","volume":"102","author":"Dover","year":"1994","journal-title":"Histochemistry"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1002\/1097-0142(19941001)74:7<1921::AID-CNCR2820740716>3.0.CO;2-9","article-title":"Correlation between the bromodeoxyuridine labeling index and the Mib-1 and Ki-67 proliferating cell indices in cerebral gliomas","volume":"74","author":"Onda","year":"1994","journal-title":"Cancer"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/4\/777\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:32:04Z","timestamp":1760207524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/4\/777"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,6]]},"references-count":75,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,4]]}},"alternative-id":["ijms18040777"],"URL":"https:\/\/doi.org\/10.3390\/ijms18040777","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,6]]}}}