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The aggregation process and aggregates are possible targets of therapeutic intervention in HD. Owing to the lack of treatment and cure, the patients die within 15\u201320 years after the disease onset. Therefore, discovering therapeutic molecules that may either inhibit the aggregation mechanism or downregulate the toxic effects of mHtt are highly needed. This study demonstrates the design and use of peptide inhibitors based on the role played by the N\u2010terminal seventeen amino acid sequence (NT<jats:sub>17<\/jats:sub>) of huntingtin fragment in its aggregation. <jats:italic>Fug\u2010<\/jats:italic>NT<jats:sub>17<\/jats:sub> (Fugu), <jats:italic>Xen\u2010<\/jats:italic>NT<jats:sub>17<\/jats:sub> (Xenopus), <jats:italic>Dro\u2010<\/jats:italic>NT<jats:sub>17<\/jats:sub> (Drosophila), Aib\u2010NT<jats:sub>17<\/jats:sub>, and Pro\u2010NT<jats:sub>17<\/jats:sub> sequences were tested for their ability to inhibit aggregation. Among them, the first three are the sequence variants of human NT<jats:sub>17<\/jats:sub> from evolutionarily distant organisms and the latter two are the analogs of human NT<jats:sub>17<\/jats:sub>\u2010containing aminoisobutyric acid (Aib) and proline (Pro). Four out of five inhibited the aggregation of huntingtin fragment, NT<jats:sub>17<\/jats:sub>Q<jats:sub>35<\/jats:sub>P<jats:sub>10<\/jats:sub>K<jats:sub>2<\/jats:sub> polypeptide. Data indicate that the physicochemical properties of the inhibitors play a crucial role in exhibiting the inhibitory effect. These inhibitors can be tested in cell and animal models for the preclinical evaluation in the treating of HD.<\/jats:p>","DOI":"10.1002\/bip.23021","type":"journal-article","created":{"date-parts":[[2017,4,13]],"date-time":"2017-04-13T15:49:27Z","timestamp":1492098567000},"source":"Crossref","is-referenced-by-count":17,"title":["Inhibition of polyglutamine aggregation by <scp>SIMILAR<\/scp> huntingtin <scp>N<\/scp>\u2010terminal sequences: Prospective molecules for preclinical evaluation in Huntington's disease"],"prefix":"10.1002","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5740-5760","authenticated-orcid":false,"given":"Gunasekhar","family":"Burra","sequence":"first","affiliation":[{"name":"Department of Biological Sciences and Bioengineering Indian Institute of Technology Kanpur Kanpur 208016 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwani Kumar","family":"Thakur","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Bioengineering Indian Institute of Technology Kanpur Kanpur 208016 India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1.5.283"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80513-9"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.8.4604"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400250"},{"key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","volume":"72","author":"HDCRG","year":"1993","journal-title":"Cell"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1806"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2007.01.003"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.221451398"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00602-0"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00041.2009"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl210"},{"key":"e_1_2_6_13_1","first-page":"690","volume":"33","author":"Yero T.","year":"2008","journal-title":"Pharm Ther"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81369-0"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0893-393"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4850"},{"key":"e_1_2_6_17_1","first-page":"429","volume-title":"Huntington's Disease","author":"Bates G. 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