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CCT can inhibit amyloid fibre assembly and toxicity of the polyQ extended mutant of huntingtin, the protein responsible for Huntington\u2019s disease. This raises the possibility that CCT modulates other amyloidopathies, a still-unaddressed question. We show here that CCT inhibits amyloid fibre assembly of \u03b1-synuclein A53T, one of the mutants responsible for Parkinson\u2019s disease. We evaluated fibrillation blockade in \u03b1-synuclein A53T deletion mutants and CCT interactions of full-length A53T in distinct oligomeric states to define an inhibition mechanism specific for \u03b1-synuclein. CCT interferes with fibre assembly by interaction of its CCT\u03b6 and CCT\u03b3 subunits with the A53T central hydrophobic region (NAC). This interaction is specific to NAC conformation, as it is produced once soluble \u03b1-synuclein A53T oligomers form and blocks the reaction before fibres begin to grow. Finally, we show that this association inhibits \u03b1-synuclein A53T oligomer toxicity in neuroblastoma cells. In summary, our results and those for huntingtin suggest that CCT is a general modulator of amyloidogenesis via a specific mechanism.<\/jats:p>","DOI":"10.1038\/srep40859","type":"journal-article","created":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T08:24:06Z","timestamp":1484814246000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["The chaperonin CCT inhibits assembly of \u03b1-synuclein amyloid fibrils by a specific, conformation-dependent interaction"],"prefix":"10.1038","volume":"7","author":[{"given":"Bego\u00f1a","family":"Sot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Rubio-Mu\u00f1oz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahudrey","family":"Leal-Quintero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Mart\u00ednez-Sabando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Marcilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cintia","family":"Roodveldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Valpuesta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,19]]},"reference":[{"key":"BFsrep40859_CR1","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/0896-6273(95)90302-X","volume":"14","author":"A Iwai","year":"1995","unstructured":"Iwai, A. et al. 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