{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:50:17Z","timestamp":1790769017988,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,1,16]],"date-time":"2013-01-16T00:00:00Z","timestamp":1358294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:p>\n                    Most neurodegenerative diseases are linked to aberrant accumulation of aggregation\u2010prone proteins. Among them, Huntington's disease (HD) is caused by an expanded polyglutamine repeat stretch in the N terminus of the mutant huntingtin protein (mHTT), which gets cleaved and aggregates in the brain. Recently established human induced pluripotent stem cell\u2010derived HD neurons exhibit some disease\u2010relevant phenotypes and provide tools for HD research. However, they have limitations such as genetic heterogeneity and an absence of mHTT aggregates and lack a robust neurodegeneration phenotype. In addition, the relationship between the phenotype and mHTT levels has not been elucidated. Herein, we present a human embryonic stem cell (hESC)\u2010derived HD neuronal model expressing HT\u2010Texon1 fragments, which addresses the deficiencies enumerated above. The wild\u2010type and HD lines are derived from an isogenic background and exhibit insoluble mHTT aggregates and neurodegeneration. We also demonstrate a quantitative relationship between neurodegeneration and soluble monomeric (but not oligomeric or aggregated) mHTT levels. Reduction of ~10% of mHTT is sufficient to prevent toxicity, whereas ~90% reduction of wild\u2010type HTT is safe and well\u2010tolerated in these cells. A known HD toxicity modifier (\n                    <jats:italic>Rhes<\/jats:italic>\n                    ) showed expected rescue of neurodegeneration. Therefore, the hESC\u2010derived neuronal models complement existing induced pluripotent stem cell\u2010derived neuronal models and provide valuable tools for HD research.\u2014Lu, B., Palacino, J. A novel human embryonic stem cell\u2010derived Huntington's disease neuronal model exhibits mutant huntingtin (mHTT) aggregates and soluble mHTT\u2010dependent neurodegeneration.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    27, 1820\u20131829 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-219220","type":"journal-article","created":{"date-parts":[[2013,1,17]],"date-time":"2013-01-17T02:24:50Z","timestamp":1358389490000},"page":"1820-1829","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["A novel human embryonic stem cell\u2010derived Huntington's disease neuronal model exhibits mutant huntingtin (mHTT) aggregates and soluble mHTT\u2010dependent neurodegeneration"],"prefix":"10.1096","volume":"27","author":[{"given":"Boxun","family":"Lu","sequence":"first","affiliation":[{"name":"School of Life Sciences Fudan University Shanghai China"},{"name":"Developmental and Molecular Pathways Novartis Institutes for BioMedical Research, Inc. Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Palacino","sequence":"additional","affiliation":[{"name":"Developmental and Molecular Pathways Novartis Institutes for BioMedical Research, Inc. Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,1,16]]},"reference":[{"key":"e_1_2_7_2_1","article-title":"Senile plaque amyloid, paired helical filaments, and cerebrovascular amyloid in Alzheimer's disease are all deposits of the same protein","volume":"1","author":"Kidd M.","year":"1985","journal-title":"Lancet"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2045"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1154584"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.6.23.4992"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","DOI":"10.1186\/1750-1326-4-11","article-title":"Inducible mutant huntingtin expression in HN10 cells reproduces Huntington's disease\u2010like neuronal dysfunction","volume":"4","author":"Weiss A.","year":"2009","journal-title":"Mol. 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