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Y\u201027632 inhibits both Rho\u2010associated kinases ROCK and PRK\u20102, making its precise intracellular target uncertain. Over\u2010expression of either kinase increases Htt and AR aggregation. Three ROCK inhibitors (Y\u201027632, HA\u20101077, and H\u20101152P), and a specific ROCK inhibitory peptide reduce polyglutamine protein aggregation, as does knockdown of ROCK or PRK\u20102 by RNAi. RNAi also indicates that each kinase is required for the inhibitory effects of Y\u201027632 to manifest fully. These two actin regulatory kinases are thus involved in polyglutamine aggregation, and their simultaneous inhibition may be an important therapeutic goal.<\/jats:p>","DOI":"10.1016\/j.febslet.2008.04.009","type":"journal-article","created":{"date-parts":[[2008,4,17]],"date-time":"2008-04-17T20:35:19Z","timestamp":1208464519000},"page":"1637-1642","source":"Crossref","is-referenced-by-count":26,"title":["ROCK and PRK\u20102 mediate the inhibitory effect of Y\u201027632 on polyglutamine aggregation"],"prefix":"10.1002","volume":"582","author":[{"given":"Jieya","family":"Shao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J.","family":"Welch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc I.","family":"Diamond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,4,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/352077a0"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00697-4"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1128"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.5046"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1719"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3510095"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.4.2247"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvg019"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00107-5"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.10.5313"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl135"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(02)00191-2"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00801.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.45.32418"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(96)00811-3"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio1207-739"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-002-0370-2"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81175-7"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.5.2489"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.141.7.1625"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001032200"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.3171\/spi.2000.93.1.0094"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-15-06570.2002"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-04-01416.2003"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.05.010"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090154"},{"key":"e_1_2_6_29_1","doi-asserted-by":"crossref","unstructured":"Takanashi Y. 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