{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:53:54Z","timestamp":1790726034113,"version":"4.1.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2015,8,14]],"date-time":"2015-08-14T00:00:00Z","timestamp":1439510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0135889","type":"journal-article","created":{"date-parts":[[2015,8,14]],"date-time":"2015-08-14T18:04:43Z","timestamp":1439575483000},"page":"e0135889","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":71,"title":["Reducing GBA2 Activity Ameliorates Neuropathology in Niemann-Pick Type C Mice"],"prefix":"10.1371","volume":"10","author":[{"given":"Andr\u00e9 R. A.","family":"Marques","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Aten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roelof","family":"Ottenhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy P. A. A.","family":"van Roomen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Herrera Moro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nike","family":"Claessen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Fernanda","family":"Vinueza Veloz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuikui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanmin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Mirzaian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf G.","family":"Boot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris I.","family":"De Zeeuw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman S.","family":"Overkleeft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yildiz","family":"Yildiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes M. F. G.","family":"Aerts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,8,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0006-291X(65)90743-6","article-title":"Metabolism of glucocerebrosides. II. Evidence of an enzymatic deficiency in Gaucher\u2019s disease","volume":"18","author":"RO Brady","year":"1965","journal-title":"Biochem Biophys Res Commun"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1001\/jamaneurol.2013.1925","article-title":"A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies","volume":"70","author":"MA Nalls","year":"2013","journal-title":"JAMA Neurol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1002\/mds.25349","article-title":"The role of SCARB2 as susceptibility factor in Parkinson\u2019s disease","volume":"28","author":"F Hopfner","year":"2013","journal-title":"Mov Disord"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0925-4439(93)90090-N","article-title":"Demonstration of the existence of a second, non-lysosomal glucocerebrosidase that is not deficient in Gaucher disease","volume":"1181","author":"S Van Weely","year":"1993","journal-title":"Biochim Biophys Acta"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1074\/jbc.M610544200","article-title":"Identification of the non-lysosomal glucosylceramidase as beta-glucosidase 2","volume":"282","author":"RG Boot","year":"2007","journal-title":"J Biol Chem"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1074\/jbc.M112.414714","article-title":"The non-lysosomal beta-glucosidase GBA2 is a non-integral membrane-associated protein at the ER and Golgi","volume":"288","author":"HG Koerschen","year":"2012","journal-title":"J Biol Chem"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1007\/s10545-012-9561-3","article-title":"Increased glucocerebrosidase (GBA) 2 activity in GBA1 deficient mice brains and in Gaucher leucocytes","volume":"36","author":"DG Burke","year":"2013","journal-title":"J Inherit Metab Dis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.1073\/pnas.1400768111","article-title":"Glucocerebrosidase 2 gene deletion rescues type 1 Gaucher disease","volume":"111","author":"PK Mistry","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/1750-1172-8-151","article-title":"Functional and genetic characterization of the non-lysosomal glucosylceramidase 2 as a modifier for Gaucher disease","volume":"8","author":"Y Yildiz","year":"2013","journal-title":"Orphanet J Rare Dis"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1098\/rstb.2003.1273","article-title":"Biochemistry of glycosphingolipid storage disorders: implications for therapeutic intervention","volume":"358","author":"JM Aerts","year":"2003","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/0005-2760(83)90218-7","article-title":"Biochemical studies in Niemann-Pick disease. I. Major sphingolipids of liver and spleen","volume":"750","author":"MT Vanier","year":"1983","journal-title":"Biochim Biophys Acta"},{"key":"ref12","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":"PG Pentchev","year":"1980","journal-title":"Biochim Biophys Acta"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"17674","DOI":"10.1074\/jbc.M313517200","article-title":"Glucosylceramidase mass and subcellular localization are modulated by cholesterol in Niemann-Pick disease type C","volume":"279","author":"R Salvioli","year":"2004","journal-title":"J Biol Chem"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"5886","DOI":"10.1073\/pnas.0308456101","article-title":"Genetic evidence for nonredundant functional cooperativity between NPC1 and NPC2 in lipid transport","volume":"101","author":"DE Sleat","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1750-1172-5-16","article-title":"Niemann-Pick disease type C","volume":"5","author":"MT Vanier","year":"2010","journal-title":"Orphanet J Rare Dis"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1126\/science.277.5323.232","article-title":"Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene","volume":"277","author":"SK Loftus","year":"1997","journal-title":"Science"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1172\/JCI29224","article-title":"Mutation of beta-glucosidase 2 causes glycolipid storage disease and impaired male fertility","volume":"116","author":"Y Yildiz","year":"2006","journal-title":"J Clin Invest"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1179\/his.2010.33.1.31","article-title":"Chromogens in Multiple Immunohistochemical Staining Used for Visual Assessment and Spectral Imaging: The Colorful Future","volume":"33","author":"CM Van der Loos","year":"2010","journal-title":"J Histotech"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"12529","DOI":"10.1002\/anie.201207771","article-title":"Novel Activity-Based Probes for Broad-Spectrum Profiling of Retaining \u03b2-Exoglucosidases In Situ and In Vivo","volume":"51","author":"WW Kallemeijn","year":"2012","journal-title":"Angew Chem Int Ed Engl"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/nchembio.466","article-title":"Ultrasensitive in situ visualization of active glucocerebrosidase molecules","volume":"6","author":"MD Witte","year":"2010","journal-title":"Nat Chem Biol. Nature Publishing Group"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/nrn2698","article-title":"Cerebellar cortical organization: a one-map hypothesis","volume":"10","author":"R Apps","year":"2009","journal-title":"Nat Rev Neurosci"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.neuron.2008.03.016","article-title":"Role of olivary electrical coupling in cerebellar motor learning","volume":"58","author":"RS Van Der Giessen","year":"2008","journal-title":"Neuron"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/j.1601-183X.2011.00763.x","article-title":"The effect of an mGluR5 inhibitor on procedural memory and avoidance discrimination impairments in Fmr1 KO mice","volume":"11","author":"MF Vinueza Veloz","year":"2012","journal-title":"Genes Brain Behav"},{"key":"ref24","article-title":"Cerebellar control of gait and interlimb coordination","author":"MF Vinueza Veloz","year":"2014","journal-title":"Brain Struct Funct"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"J Folch","year":"1957","journal-title":"J Biol Chem"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.cca.2007.12.001","article-title":"Prominent increase in plasma ganglioside GM3 is associated with clinical manifestations of type I Gaucher disease","volume":"389","author":"K Ghauharali-van der Vlugt","year":"2008","journal-title":"Clin Chim Acta"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/o59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"EG Bligh","year":"1959","journal-title":"Can J Biochem Physiol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1373\/clinchem.2006.079012","article-title":"HPLC for simultaneous quantification of total ceramide, glucosylceramide, and ceramide trihexoside concentrations in plasma","volume":"53","author":"JEM Groener","year":"2007","journal-title":"Clin Chem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1182\/blood-2011-05-352971","article-title":"Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype, storage cell markers, and therapeutic response","volume":"118","author":"N Dekker","year":"2011","journal-title":"Blood"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nrn3011","article-title":"Spatiotemporal firing patterns in the cerebellum","volume":"12","author":"CI De Zeeuw","year":"2011","journal-title":"Nat Rev Neurosci. Nature Publishing Group"},{"key":"ref31","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":"JR Sarna","year":"2003","journal-title":"J Comp Neurol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.bbrc.2011.08.096","article-title":"Npc1 deficiency in the C57BL\/6J genetic background enhances Niemann-Pick disease type C spleen pathology","volume":"413","author":"J Parra","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"26522","DOI":"10.1074\/jbc.273.41.26522","article-title":"Generation of specific deoxynojirimycin-type inhibitors of the non-lysosomal glucosylceramidase","volume":"273","author":"HS Overkleeft","year":"1998","journal-title":"J Biol Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"e21758","DOI":"10.1371\/journal.pone.0021758","article-title":"Iminosugar-based inhibitors of glucosylceramide synthase increase brain glycosphingolipids and survival in a mouse model of sandhoff disease","volume":"6","author":"KM Ashe","year":"2011","journal-title":"PLoS One"},{"key":"ref35","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":"S Sarkar","year":"2013","journal-title":"Cell Rep"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/s10545-006-0411-z","article-title":"Glucosylceramide transfer from lysosomes-the missing link in molecular pathology of glucosylceramidase deficiency: a hypothesis based on existing data","volume":"29","author":"M Elleder","year":"2006","journal-title":"J Inherit Metab Dis"},{"key":"ref37","first-page":"498","article-title":"The nonlysosomal \u03b2-glucosidase GBA2 promotes endoplasmic reticulum stress and impairs tumorigenicity of human melanoma cells","volume":"27","author":"S-C Sorli","year":"2012","journal-title":"FASEB J"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"8362","DOI":"10.1016\/S0021-9258(17)37202-2","article-title":"N-butyldeoxynojirimycin is a novel inhibitor of glycolipid biosynthesis","volume":"269","author":"FM Platt","year":"1994","journal-title":"J Biol Chem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/S0140-6736(00)02161-9","article-title":"Novel oral treatment of Gaucher\u2019s disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis","volume":"355","author":"T Cox","year":"2000","journal-title":"Lancet"},{"key":"ref40","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":"M Zervas","year":"2001","journal-title":"Curr Biol"},{"key":"ref41","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":"MC Patterson","year":"2007","journal-title":"Lancet Neurol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1021\/jo061280p","article-title":"Development of adamantan-1-yl-methoxy-functionalized 1-deoxynojirimycin derivatives as selective inhibitors of glucosylceramide metabolism in man","volume":"72","author":"T Wennekes","year":"2007","journal-title":"J Org Chem"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.ymgme.2012.01.020","article-title":"Iminosugar-based inhibitors of glucosylceramide synthase prolong survival but paradoxically increase brain glucosylceramide levels in Niemann-Pick C mice","volume":"105","author":"JB Nietupski","year":"2012","journal-title":"Mol Genet Metab"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0135889","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T13:03:28Z","timestamp":1653051808000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0135889"}},"subtitle":[],"editor":[{"given":"Andrea","family":"Dardis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,8,14]]},"references-count":43,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2015,8,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0135889","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,14]]}}}