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Since the diversity and sizes of the soluble Htt-polyQ aggregates that have been linked to cytotoxicity are unknown, we investigated soluble Htt-polyQ aggregates using analytical ultracentrifugation. Soon after induction in a yeast HD model system, non-toxic Htt-25Q and cytotoxic Htt-103Q both formed soluble aggregates 29S to 200S in size. Because current models indicate that Htt-25Q does not form soluble aggregates, reevaluation of previous studies may be necessary. Only Htt-103Q aggregation behavior changed, however, with time. At 6\u2009hr mid-sized aggregates (33S to 84S) and large aggregates (greater than 100S) became present while at 24\u2009hr primarily only mid-sized aggregates (20S to 80S) existed. Multiple factors that decreased cytotoxicity of Htt-103Q (changing the length of or sequences adjacent to the polyQ, altering ploidy or chaperone dosage, or deleting anti-aging factors) altered the Htt-103Q aggregation pattern in which the suite of mid-sized aggregates at 6\u2009hr were most correlative with cytotoxicity. Hence, the amelioration of HD and other neurodegenerative diseases may require increased attention to and discrimination of the dynamic alterations in soluble aggregation processes.<\/jats:p>","DOI":"10.1038\/srep34916","type":"journal-article","created":{"date-parts":[[2016,10,10]],"date-time":"2016-10-10T11:29:29Z","timestamp":1476098969000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Multiple discrete soluble aggregates influence polyglutamine toxicity in a Huntington\u2019s disease model system"],"prefix":"10.1038","volume":"6","author":[{"given":"Wen","family":"Xi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"Laue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clyde L.","family":"Denis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,10,10]]},"reference":[{"key":"BFsrep34916_CR1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1602\/neurorx.1.2.255","volume":"1","author":"RH Myers","year":"2004","unstructured":"Myers, R. 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