{"id":49950,"date":"2019-02-28T00:00:00","date_gmt":"2019-02-28T00:00:00","guid":{"rendered":"https:\/\/www.cpr.cuhk.edu.hk\/press\/cuhk-discovers-new-inhibitors-to-restrain-neurodegenerationshedding-light-on-treating-polyq-diseases\/"},"modified":"2019-02-28T00:00:00","modified_gmt":"2019-02-28T00:00:00","slug":"cuhk-discovers-new-inhibitors-to-restrain-neurodegenerationshedding-light-on-treating-polyq-diseases","status":"publish","type":"press","link":"https:\/\/www.cpr.cuhk.edu.hk\/tc\/press\/cuhk-discovers-new-inhibitors-to-restrain-neurodegenerationshedding-light-on-treating-polyq-diseases\/","title":{"rendered":"\u4e2d\u5927\u7814\u767c\u795e\u7d93\u9000\u5316\u6027\u75be\u75c5\u6291\u5236\u5291\u70ba\u6cbb\u7642polyQ\u75be\u75c5\u5e36\u4f86\u66d9\u5149"},"content":{"rendered":"","protected":false},"featured_media":0,"template":"","tags":[],"class_list":["post-49950","press","type-press","status-publish","hentry"],"acf":{"title_alt":"","sub_title_alt":"","press_date":"20190228","keep":false,"details":"<p>\u9999\u6e2f\u4e2d\u6587\u5927\u5b78\uff08\u4e2d\u5927\uff09\u751f\u547d\u79d1\u5b78\u5b78\u9662\u6559\u6388<strong>\u9673\u6d69\u7136\u6559\u6388<\/strong>\u53ca\u5176\u7814\u7a76\u5c0f\u7d44\u767c\u73fe\u4e86\u4e00\u7a2e\u540d\u70baAnti-polyQ Aggregation for Machado-Joseph-Associated Neurodegeneration\uff08AQAMAN\uff09\u7684\u5c0f\u5206\u5b50\u5316\u5408\u7269\uff0c\u80fd\u6709\u6548\u89e3\u96e2\u6709\u6bd2\u86cb\u767d\u8cea\u805a\u96c6\u9ad4\uff0c\u6291\u5236\u795e\u7d93\u9000\u5316\u3002AQAMAN\u53ef\u671b\u88ab\u958b\u767c\u6210\u85e5\u7269\uff0c\u7528\u4f5c\u6cbb\u7642\u99ac\u67e5\u591a&ndash;\u7d04\u745f\u592b\u75c5\uff08Machado-Joseph Disease\uff0c\u4e00\u7a2e\u6700\u5e38\u898b\u7684\u810a\u9ad3\u5c0f\u8166\u6027\u5171\u6fdf\u5931\u8abf\uff0c\u7c21\u7a31\u5c0f\u8166\u840e\u7e2e\u75c7\u6216SCAs\uff09\u53ca\u5176\u4ed6\u591a\u805a\u8c37\u6c28\u9170\u80fa\uff08polyQ\uff09\u75be\u75c5\uff0c\u70ba\u60a3\u6709\u9019\u985e\u75be\u75c5\u7684\u75c5\u4eba\u5e36\u4f86\u65b0\u5e0c\u671b\u3002\u9673\u6559\u6388\u7684\u7814\u7a76\u6210\u679c\u6700\u8fd1\u7372\u300a\u751f\u7269\u5316\u5b78\u671f\u520a\u300b\uff08<em>Journal of Biological Chemistry<\/em>\uff09\u4f5c\u70ba\u5c01\u9762\u6587\u7ae0\u767c\u8868\u3002<\/p><p>\u81ea1999\u5e74\uff0c\u9673\u6559\u6388\u4e00\u76f4\u7814\u7a76polyQ\u75be\u75c5\uff08\u4e00\u7d44\u7f55\u898b\u7684\u795e\u7d93\u7cfb\u7d71\u75be\u75c5\uff0c\u5305\u62ecSCAs\uff09\uff0c\u4e26\u958b\u767c\u91dd\u5c0d\u9019\u4e9b\u75be\u75c5\u7684\u6cbb\u7642\u5e72\u9810\u63aa\u65bd\u3002SCAs\u4ee4\u75c5\u4eba\u5c0f\u8166\u4e2d\u7684\u795e\u7d93\u7d30\u80de\u9010\u6f38\u6b7b\u4ea1\uff0c\u4ee5\u81f4\u624b\u8173\u808c\u8089\u5931\u53bb\u63a7\u5236\u3001\u6b65\u614b\u4e0d\u7a69\u3001\u8a00\u8a9e\u4e0d\u6e05\u7b49\u3002\u4e00\u822c\u800c\u8a00\uff0cpolyQ\u75be\u75c5\u60a3\u8005\u5c07\u9010\u6f38\u55aa\u5931\u7cbe\u7d30\u904b\u52d5\u529f\u80fd\uff0c\u96e3\u4ee5\u4fdd\u6301\u5e73\u8861\u6216\u5354\u8abf\u65e5\u5e38\u904b\u52d5\u3002\u8fc4\u4eca\u70ba\u6b62\uff0cpolyQ\u75be\u75c5\u4ecd\u7136\u7121\u6cd5\u6cbb\u7652\u3002<\/p><p><strong>\u4e2d\u5927\u767c\u73fe<\/strong><strong>AQAMAN<\/strong><strong>\u6709\u52a9\u6cbb\u7642<\/strong><strong>polyQ<\/strong><strong>\u75be\u75c5<\/strong><\/p><p>\u9673\u6559\u6388\u8207\u4f86\u81ea\u4e39\u9ea5\u3001\u6cd5\u570b\u3001\u610f\u5927\u5229\u3001\u82f1\u570b\u548c\u7f8e\u570b\u7684\u7814\u7a76\u4eba\u54e1\u5c55\u958b\u4e86\u570b\u969b\u7814\u7a76\u5408\u4f5c\uff0c\u5171\u540c\u7ba1\u7406\u6709\u95dcSCAs\u53ca\u5176\u4ed6\u7f55\u898b\u795e\u7d93\u8207\u795e\u7d93\u808c\u8089\u75be\u75c5\u7684\u591a\u5b78\u79d1\u7814\u7a76\u9805\u76ee\uff0c\u7576\u4e2d\u4ed6\u8207Steven C. Zimmerman\u6559\u6388\uff08\u7f8e\u570b\u4f0a\u5229\u8afe\u4f0a\u5927\u5b78\u5384\u5df4\u7d0d&ndash;\u9999\u6ab3\u5206\u6821\uff09\u7dca\u5bc6\u5408\u4f5c\u3002Zimmerman\u6559\u6388\u662f\u5408\u6210\u5316\u5b78\u5c08\u5bb6\uff0c\u5c08\u6ce8\u65bc\u7be9\u9078\u91dd\u5c0d\u7f55\u898b\u75be\u75c5\uff08\u5305\u62ecSCAs\u548c\u5f37\u76f4\u6027\u808c\u8089\u71df\u990a\u4e0d\u826f\u75c7\uff09\u7684\u5019\u9078\u85e5\u7269\u3002\u5c0f\u5206\u5b50\u5316\u5408\u7269AQAMAN\u4fbf\u662f\u7531Zimmerman\u6559\u6388\u7684\u5718\u968a\u751f\u7522\uff0c\u539f\u5b9a\u7528\u65bc\u6cbb\u7642\u5f37\u76f4\u6027\u808c\u8089\u71df\u990a\u4e0d\u826f\u75c7\uff08\u4e00\u7d44\u808c\u8089\u840e\u7f29\uff0f\u9000\u5316\u75be\u75c5\uff09\u3002\u9673\u6559\u6388\u7684\u5718\u968a\u5076\u7136\u767c\u73feAQAMAN\u5c0dpolyQ\u75be\u75c5\u4ea6\u6709\u6f5b\u5728\u7642\u6548\u3002PolyQ\u75be\u75c5\u662f\u4e00\u7d44\u7531\u86cb\u767d\u8cea\u805a\u5408\u9ad4\u5f15\u767c\u7684\u795e\u7d93\u9000\u884c\u6027\u75be\u75c5\uff0c\u800cAQAMAN\u80fd\u5e72\u64fepolyQ\u86cb\u767d\u8cea\u805a\u5408\u9ad4\u5f62\u6210\uff0c\u4e26\u4fc3\u4f7f\u5df2\u5f62\u6210\u7684\u805a\u5408\u9ad4\u5206\u89e3\u3002\u9673\u6559\u6388\u7684\u5718\u968a\u76ee\u524d\u6b63\u5728\u5c0b\u6c42\u85e5\u5ee0\u70ba\u5408\u4f5c\u5925\u4f34\uff0c\u4ee5\u9032\u4e00\u6b65\u6539\u5584AQAMAN\u7684\u85e5\u6027\u3002<\/p><p>\u9673\u6559\u6388\u8aaa\uff1a\u300c\u932f\u8aa4\u6298\u758a\u548c\u805a\u96c6\u7684\u86cb\u767d\u8cea\u8207\u591a\u7a2e\u4eba\u985e\u75be\u75c5\u5bc6\u5207\u76f8\u95dc\u3002\u81ea1999\u5e74\u4ee5\u4f86\uff0c\u6211\u4e00\u76f4\u7814\u7a76polyQ\u86cb\u767d\u805a\u5408\u9ad4\u5982\u4f55\u5c0e\u81f4\u795e\u7d93\u7d30\u80de\u9000\u5316\uff0c\u4e26\u8a66\u5716\u4ee5\u907a\u50b3\u7b56\u7565\u4f86\u5e72\u9810\u6709\u6bd2polyQ\u805a\u5408\u9ad4\u7684\u5f62\u6210\u3002\u81ea2012\u5e74\u8d77\uff0c\u6211\u8207Zimmerman\u6559\u6388\u5408\u4f5c\uff0c\u4f7f\u7528\u679c\u8805<em>Drosophila<\/em>\u4f5c\u70ba\u85e5\u7269\u7be9\u9078\u6a21\u578b\uff0c\u7528\u4f86\u6e2c\u8a66\u53ca\u8a55\u4f30\u4e0d\u540c\u7684\u5c0f\u5206\u5b50\u5316\u5408\u7269\u5c0d\u91ab\u6cbb\u5f37\u76f4\u6027\u808c\u8089\u71df\u990a\u4e0d\u826f\u75c7\u7684\u6548\u679c\u3002\u5f8c\u4f86\u57282016\u5e74\uff0c\u6211\u8207\u7ba1\u9032\u6559\u6388\uff08\u4e2d\u5927\u751f\u547d\u79d1\u5b78\u5b78\u9662\uff09\u5408\u4f5c\uff0c\u4f7f\u7528\u679c\u8805\u7684\u795e\u7d93\u808c\u8089\u63a5\u982d\u4f86\u7814\u7a76\u5f37\u76f4\u6027\u808c\u8089\u71df\u990a\u4e0d\u826f\u75c7\u7684\u75be\u75c5\u6a5f\u5236\u3002AQAMAN\u662f\u773e\u591a\u57fa\u65bc\u96d9\u8112\u7684\u6291\u5236\u5291\u4e4b\u4e00\uff0c\u539f\u672c\u662f\u7528\u4f86\u6291\u5236\u5f37\u76f4\u6027\u808c\u8089\u71df\u990a\u4e0d\u826f\u75c7\u4e2d\u7684\u6838\u7cd6\u6838\u9178&ndash;\u86cb\u767d\u8907\u5408\u7269\u3002\u4f46\u51fa\u4e4e\u6211\u5011\u9810\u671f\uff0cAQAMAN\u7adf\u7136\u5177\u6709\u5e72\u64fe\u6709\u6bd2\u86cb\u767d\u8cea\u805a\u96c6\u7684\u80fd\u529b\u3002\u6211\u5011\u5e0c\u671b\u9032\u4e00\u6b65\u7814\u767cAQAMAN\u4f5c\u81e8\u5e8a\u6cbb\u7642\u7528\u9014\uff0c\u70bapolyQ\u75be\u75c5\u60a3\u8005\u5e36\u4f86\u5e0c\u671b\u3002\u300d<\/p><p>\u662f\u9805\u7814\u7a76\u7372\u4e2d\u5927\u6821\u9577\u5099\u7528\u57fa\u91d1\u3001\u4e2d\u5927\u5442\u5fd7\u548c\u5275\u65b0\u91ab\u5b78\u7814\u7a76\u6240\u3001\u4e2d\u5927\u8521\u6c38\u696d\u8166\u795e\u7d93\u79d1\u5b78\u4e2d\u5fc3\u3001\u88d8\u69ce\u57fa\u91d1\u6703\u3001\u7f8e\u570b\u570b\u5bb6\u885e\u751f\u7814\u7a76\u9662\uff0c\u4ee5\u53ca\u9999\u6e2f\u5c0f\u8166\u840e\u7e2e\u75c7\u5354\u6703\u7684\u6350\u6b3e\u8cc7\u52a9\u3002<\/p><p><strong>\u6539\u826f\u578b\u591a\u80bd\u6291\u5236\u5291\u80fd\u5c0d\u6297\u795e\u7d93\u9000\u5316\u75be\u75c5\u7684<\/strong><strong> RNA<\/strong><strong>\u6bd2\u6027<\/strong><\/p><p>2016\u5e74\uff0c\u9673\u6559\u6388\u8207\u4e2d\u5927\u751f\u547d\u79d1\u5b78\u5b78\u9662\u6556\u5fd7\u797a\u6559\u6388\u5408\u4f5c\uff0c\u81f4\u529b\u958b\u767c\u4e00\u7a2e\u65b0\u578b\u591a\u80bd\u6291\u5236\u5291\uff0c\u7528\u65bc\u62b5\u6297polyQ\u75be\u75c5\u7684CAG RNA\u6bd2\u6027\u3002\u6556\u6559\u6388\u662f\u4e00\u4f4d\u7d50\u69cb\u751f\u7269\u5b78\u5bb6\u548c\u8cc7\u6df1\u7684\u85e5\u7269\u7814\u767c\u5c08\u5bb6\u3002\u5718\u968a\u6700\u8fd1\u767c\u73fe\u4e86\u4e00\u7a2e\u753121\u500b\u6c28\u57fa\u9178\u7d44\u6210\u7684\u591a\u80bd\u5206\u5b50\uff0c\u4f5c\u70ba\u7528\u65bc\u795e\u7d93\u9000\u5316\u6027\u75be\u75c5\u7684\u6539\u826f\u578b\u591a\u80bd\u6291\u5236\u5291\uff0c\u4e26\u547d\u540d\u70baBIND\u3002\u9019\u7a2e\u6291\u5236\u5291\u80fd\u91dd\u5c0dpolyQ\u75be\u75c5\u548cC9orf72-\u76f8\u95dc\u7684\u808c\u840e\u7f29\u6027\u810a\u9ad3\u5074\u7d22\u786c\u5316\u75c7\uff08\u53c8\u540d\u6f38\u51cd\u4eba\u75c7\uff09\/ \u984d\u9873\u8449\u578b\u5931\u667a\u75c7\uff08C9ALS \/ FTD\uff09\u7684RNA\u6bd2\u6027\u3002\u6709\u95dcpolyQ\u548cC9ALS \/ FTD\u7684\u767c\u73fe\u5df2\u5206\u5225\u5728<em>RNA<\/em> \u53ca<em>Molecular Therapy<\/em><em>&ndash;<\/em><em>Nucleic Acids<\/em>\u5169\u672c\u671f\u520a\u4e2d\u767c\u8868\uff08Zhang et al., (2018); Zhang et al., (2019) \u5370\u88fd\u4e2d\uff09\u3002<\/p><p>\u6556\u6559\u6388\u8aaa\uff1a\u300c\u81ea2016\u5e74\u4ee5\u4f86\uff0c\u9673\u6559\u6388\u548c\u6211\u4e00\u76f4\u52aa\u529b\u9032\u4e00\u6b65\u512a\u5316\u6211\u5011\u7684\u591a\u80bd\u985eRNA\u6bd2\u6027\u6291\u5236\u5291\u3002polyQ\u75be\u75c5\u4e2d\u7684RNA\u6bd2\u6027\u7531CAG\u91cd\u8907\u64f4\u589e\u5f15\u8d77\uff0c\u800cC9ALS \/ FTD\u4e2d\u7684RNA\u6bd2\u6027\u5247\u7531GGGGCC\u91cd\u8907\u64f4\u589e\u5f15\u8d77\u3002GGGGCC\u662f\u5728\u4eba\u985e\u57fa\u56e0\u7d44\u4e2d\u7684\u4e00\u7a2e\u516d\u6838\u82f7\u9178\u91cd\u8907DNA\u5e8f\u5217\uff0c\u4e0d\u53d7\u63a7\u5236\u7684GGGGCC\u91cd\u8907\u64f4\u589e\u6703\u5c0e\u81f4C9ALS \/ FTD\u7f55\u898b\u75be\u75c5\u3002\u5118\u7ba1polyQ\u548cC9ALS \/ 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