{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T14:06:12Z","timestamp":1783951572118,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T00:00:00Z","timestamp":1667433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20ek0109460"],"award-info":[{"award-number":["JP20ek0109460"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K07785"],"award-info":[{"award-number":["JP21K07785"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fabry disease (FD) is an X\u2010linked inherited lysosomal metabolism disorder in which globotriaosylceramide (Gb3) accumulates in various organs resulting from a deficiency in alpha\u2010galactosidase A. The clinical features of FD include progressive impairments of the renal, cardiac, and peripheral nervous systems. In addition, patients with FD often develop neuropsychiatric symptoms, such as depression and dementia, which are believed to be induced by the cellular injury of cerebrovascular and partially neuronal cells due to Gb3 accumulation. Although the analysis of autopsy brain tissue from patients with FD showed no accumulation of Gb3, abnormal deposits of Gb3 were found in the neurons of several brain areas, including the hippocampus. Therefore, in this study, we generated induced pluripotent stem cells (iPSCs) from patients with FD and differentiated them into neuronal cells to investigate pathological and biological changes in the neurons of FD. Neural stem cells (NSCs) and neurons were successfully differentiated from the iPSCs we generated; however, cellular damage and morphological changes were not found in these cells. Immunostaining revealed no Gb3 accumulation in NSCs and neurons. Transmission electron microscopy did not reveal any zebra body\u2010like structures or inclusion bodies, which are characteristic of FD. These results indicated that neuronal cells derived from FD\u2010iPSCs exhibited normal morphology and no Gb3 accumulation. It is likely that more in vivo environment\u2010like cultures are needed for iPSC\u2010derived neurons to reproduce disease\u2010specific features.<\/jats:p>","DOI":"10.1002\/jimd.12567","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T02:24:09Z","timestamp":1665541449000},"page":"143-152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Characterization of cellular phenotypes in neurons derived from induced pluripotent stem cells of male patients with Fabry disease"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2125-8401","authenticated-orcid":false,"given":"Takashi","family":"Miyajima","sequence":"first","affiliation":[{"name":"Advanced Clinical Research Center Southern Tohoku Research Institute for Neuroscience  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Saito","sequence":"additional","affiliation":[{"name":"Advanced Clinical Research Center Southern Tohoku Research Institute for Neuroscience  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Yanagisawa","sequence":"additional","affiliation":[{"name":"Advanced Clinical Research Center Southern Tohoku Research Institute for Neuroscience  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Advanced Clinical Research Center Southern Tohoku Research Institute for Neuroscience  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wu","sequence":"additional","affiliation":[{"name":"Advanced Clinical Research Center Southern Tohoku Research Institute for Neuroscience  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Division of Molecular Cell Biology, Core Research Facilities for Basic Science The Jikei University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikatsu","family":"Eto","sequence":"additional","affiliation":[{"name":"Advanced Clinical Research Center Southern Tohoku Research Institute for Neuroscience  Kawasaki Japan"},{"name":"The Jikei University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2004.01309.x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-013-9643-x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-007-0708-6"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01606034"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.11.004"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-007-0468-6"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00697017"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00690579"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1973.00490220039004"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.06.003"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2013-0080"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"issue":"2","key":"e_1_2_11_15_1","first-page":"157","article-title":"Fabry's disease: enzymatic diagnosis of hemizygotes and heterozygotes. Alpha\u2010galactosidase activities in plasma, serum, urine, and leukocytes","volume":"81","author":"Desnick RJ","year":"1973","journal-title":"J Lab Clin Med"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2021.100784"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2004.03.003"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6.5.11943"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2019.03.003"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.06.016"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.02.003"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.09.004"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.07.004"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2018.07.246"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102633"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052381"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.526293"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67635-0"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2016.02.019"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400105"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20423"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(06)70548-8"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002673"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368916X694265"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2022.100852"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1917"},{"issue":"5","key":"e_1_2_11_37_1","first-page":"446","article-title":"Murine models of lysosomal storage diseases exhibit differences in brain protein aggregation and neuroinflammation","volume":"9","author":"Clarke J","year":"2021","journal-title":"Biomedicine"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlz139"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0901281"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz205"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa064"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02266-7"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy147"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12567","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.12567","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12567","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T20:41:04Z","timestamp":1692564064000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.12567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,3]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1002\/jimd.12567"],"URL":"https:\/\/doi.org\/10.1002\/jimd.12567","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,3]]},"assertion":[{"value":"2022-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}