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Expression of an expanded polyglutamine repeat within the Huntingtin (Htt) protein impacts numerous cellular processes, including protein folding and clearance. A hallmark of the disease is the progressive formation of inclusions that represent the culmination of a complex aggregation process. Methylene blue (MB), has been shown to modulate aggregation of amyloidogenic disease proteins. We investigated whether MB could impact mutant Htt-mediated aggregation and neurotoxicity. MB inhibited recombinant protein aggregation<jats:italic>in vitro<\/jats:italic>, even when added to preformed oligomers and fibrils. MB also decreased oligomer number and size and decreased accumulation of insoluble mutant Htt in cells. In functional assays, MB increased survival of primary cortical neurons transduced with mutant Htt, reduced neurodegeneration and aggregation in a<jats:italic>Drosophila melanogaster<\/jats:italic>model of HD, and reduced disease phenotypes in<jats:italic>R6\/2<\/jats:italic>HD modeled mice. Furthermore, MB treatment also promoted an increase in levels of BDNF RNA and protein<jats:italic>in vivo<\/jats:italic>. Thus, MB, which is well tolerated and used in humans, has therapeutic potential for HD.<\/jats:p>","DOI":"10.1523\/jneurosci.0895-12.2012","type":"journal-article","created":{"date-parts":[[2012,8,8]],"date-time":"2012-08-08T16:54:11Z","timestamp":1344444851000},"page":"11109-11119","source":"Crossref","is-referenced-by-count":91,"title":["Methylene Blue Modulates Huntingtin Aggregation Intermediates and Is Protective in Huntington's Disease Models"],"prefix":"10.1523","volume":"32","author":[{"given":"Emily Mitchell","family":"Sontag","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor P.","family":"Lotz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namita","family":"Agrawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Aron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guocheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Necula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Finkbeiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Glabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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