{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:45:54Z","timestamp":1767962754430,"version":"3.49.0"},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,5,26]],"date-time":"2015-05-26T00:00:00Z","timestamp":1432598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["2010-020272(3)"],"award-info":[{"award-number":["2010-020272(3)"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">GM1<\/jats:styled-content> gangliosidosis (<jats:styled-content style=\"fixed-case\">GM1<\/jats:styled-content>) is an inherited neurodegenerative disorder caused by mutations in the lysosomal \u03b2\u2010galactosidase (\u03b2\u2010gal) gene. Insufficient \u03b2\u2010gal activity leads to abnormal accumulation of <jats:styled-content style=\"fixed-case\">GM1<\/jats:styled-content> gangliosides in tissues, particularly in the central nervous system, resulting in progressive neurodegeneration. Here, we report an <jats:italic>in vitro<\/jats:italic> human <jats:styled-content style=\"fixed-case\">GM1<\/jats:styled-content> model, based on induced pluripotent stem cell (<jats:styled-content style=\"fixed-case\">iPSC<\/jats:styled-content>) technology. Neural progenitor cells differentiated from <jats:styled-content style=\"fixed-case\">GM1<\/jats:styled-content> patient\u2010derived <jats:styled-content style=\"fixed-case\">iPSCs<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">GM1\u2010NPCs<\/jats:styled-content>) recapitulated the biochemical and molecular phenotypes of <jats:styled-content style=\"fixed-case\">GM1<\/jats:styled-content>, including defective \u03b2\u2010gal activity and increased lysosomes. Importantly, the characterization of <jats:styled-content style=\"fixed-case\">GM1\u2010NPCs<\/jats:styled-content> established that <jats:styled-content style=\"fixed-case\">GM1<\/jats:styled-content> is significantly associated with the activation of inflammasomes, which play a critical role in the pathogenesis of various neurodegenerative diseases. Specific inflammasome inhibitors potently alleviated the disease\u2010related phenotypes of <jats:styled-content style=\"fixed-case\">GM1\u2010NPCs<\/jats:styled-content> <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Our data demonstrate that <jats:styled-content style=\"fixed-case\">GM1\u2010NPCs<\/jats:styled-content> are a valuable <jats:italic>in vitro<\/jats:italic> human <jats:styled-content style=\"fixed-case\">GM1<\/jats:styled-content> model and suggest that inflammasome activation is a novel target pathway for <jats:styled-content style=\"fixed-case\">GM1<\/jats:styled-content> drug development. Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4551","type":"journal-article","created":{"date-parts":[[2015,4,29]],"date-time":"2015-04-29T23:52:56Z","timestamp":1430351576000},"page":"98-110","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["A novel human model of the neurodegenerative disease <scp>GM1<\/scp> gangliosidosis using induced pluripotent stem cells demonstrates inflammasome activation"],"prefix":"10.1002","volume":"237","author":[{"given":"Mi\u2010Young","family":"Son","sequence":"first","affiliation":[{"name":"Stem Cell Research Centre Korea Research Institute of Bioscience and Biotechnology (KRIBB)  Daejeon Republic of Korea"},{"name":"Department of Functional Genomics University of Science and Technology  Daejeon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Eun","family":"Kwak","sequence":"additional","affiliation":[{"name":"Stem 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