{"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\/sc\/press\/cuhk-discovers-new-inhibitors-to-restrain-neurodegenerationshedding-light-on-treating-polyq-diseases\/","title":{"rendered":"\u4e2d\u5927\u7814\u53d1\u795e\u7ecf\u9000\u5316\u6027\u75be\u75c5\u6291\u5236\u5242\u4e3a\u6cbb\u7597polyQ\u75be\u75c5\u5e26\u6765\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\u5b66\uff08\u4e2d\u5927\uff09\u751f\u547d\u79d1\u5b66\u5b66\u9662\u6559\u6388<strong>\u9648\u6d69\u7136\u6559\u6388<\/strong>\u53ca\u5176\u7814\u7a76\u5c0f\u7ec4\u53d1\u73b0\u4e86\u4e00\u79cd\u540d\u4e3aAnti-polyQ Aggregation for Machado-Joseph-Associated Neurodegeneration\uff08AQAMAN\uff09\u7684\u5c0f\u5206\u5b50\u5316\u5408\u7269\uff0c\u80fd\u6709\u6548\u89e3\u79bb\u6709\u6bd2\u86cb\u767d\u8d28\u805a\u96c6\u4f53\uff0c\u6291\u5236\u795e\u7ecf\u9000\u5316\u3002AQAMAN\u53ef\u671b\u88ab\u5f00\u53d1\u6210\u836f\u7269\uff0c\u7528\u4f5c\u6cbb\u7597\u9a6c\u67e5\u591a&ndash;\u7ea6\u745f\u592b\u75c5\uff08Machado-Joseph Disease\uff0c\u4e00\u79cd\u6700\u5e38\u89c1\u7684\u810a\u9ad3\u5c0f\u8111\u6027\u5171\u6d4e\u5931\u8c03\uff0c\u7b80\u79f0\u5c0f\u8111\u840e\u7f29\u75c7\u6216SCAs\uff09\u53ca\u5176\u4ed6\u591a\u805a\u8c37\u6c28\u9170\u80fa\uff08polyQ\uff09\u75be\u75c5\uff0c\u4e3a\u60a3\u6709\u8fd9\u7c7b\u75be\u75c5\u7684\u75c5\u4eba\u5e26\u6765\u65b0\u5e0c\u671b\u3002\u9648\u6559\u6388\u7684\u7814\u7a76\u6210\u679c\u6700\u8fd1\u83b7\u300a\u751f\u7269\u5316\u5b66\u671f\u520a\u300b\uff08<em>Journal of Biological Chemistry<\/em>\uff09\u4f5c\u4e3a\u5c01\u9762\u6587\u7ae0\u53d1\u8868\u3002<\/p><p>\u81ea1999\u5e74\uff0c\u9648\u6559\u6388\u4e00\u76f4\u7814\u7a76polyQ\u75be\u75c5\uff08\u4e00\u7ec4\u7f55\u89c1\u7684\u795e\u7ecf\u7cfb\u7edf\u75be\u75c5\uff0c\u5305\u62ecSCAs\uff09\uff0c\u5e76\u5f00\u53d1\u9488\u5bf9\u8fd9\u4e9b\u75be\u75c5\u7684\u6cbb\u7597\u5e72\u9884\u63aa\u65bd\u3002SCAs\u4ee4\u75c5\u4eba\u5c0f\u8111\u4e2d\u7684\u795e\u7ecf\u7ec6\u80de\u9010\u6e10\u6b7b\u4ea1\uff0c\u4ee5\u81f4\u624b\u811a\u808c\u8089\u5931\u53bb\u63a7\u5236\u3001\u6b65\u6001\u4e0d\u7a33\u3001\u8a00\u8bed\u4e0d\u6e05\u7b49\u3002\u4e00\u822c\u800c\u8a00\uff0cpolyQ\u75be\u75c5\u60a3\u8005\u5c06\u9010\u6e10\u4e27\u5931\u7cbe\u7ec6\u8fd0\u52a8\u529f\u80fd\uff0c\u96be\u4ee5\u4fdd\u6301\u5e73\u8861\u6216\u534f\u8c03\u65e5\u5e38\u8fd0\u52a8\u3002\u8fc4\u4eca\u4e3a\u6b62\uff0cpolyQ\u75be\u75c5\u4ecd\u7136\u65e0\u6cd5\u6cbb\u6108\u3002<\/p><p><strong>\u4e2d\u5927\u53d1\u73b0<\/strong><strong>AQAMAN<\/strong><strong>\u6709\u52a9\u6cbb\u7597<\/strong><strong>polyQ<\/strong><strong>\u75be\u75c5<\/strong><\/p><p>\u9648\u6559\u6388\u4e0e\u6765\u81ea\u4e39\u9ea6\u3001\u6cd5\u56fd\u3001\u610f\u5927\u5229\u3001\u82f1\u56fd\u548c\u7f8e\u56fd\u7684\u7814\u7a76\u4eba\u5458\u5c55\u5f00\u4e86\u56fd\u9645\u7814\u7a76\u5408\u4f5c\uff0c\u5171\u540c\u7ba1\u7406\u6709\u5173SCAs\u53ca\u5176\u4ed6\u7f55\u89c1\u795e\u7ecf\u4e0e\u795e\u7ecf\u808c\u8089\u75be\u75c5\u7684\u591a\u5b66\u79d1\u7814\u7a76\u9879\u76ee\uff0c\u5f53\u4e2d\u4ed6\u4e0eSteven C. Zimmerman\u6559\u6388\uff08\u7f8e\u56fd\u4f0a\u5229\u8bfa\u4f0a\u5927\u5b66\u5384\u5df4\u7eb3&ndash;\u9999\u69df\u5206\u6821\uff09\u7d27\u5bc6\u5408\u4f5c\u3002Zimmerman\u6559\u6388\u662f\u5408\u6210\u5316\u5b66\u4e13\u5bb6\uff0c\u4e13\u6ce8\u4e8e\u7b5b\u9009\u9488\u5bf9\u7f55\u89c1\u75be\u75c5\uff08\u5305\u62ecSCAs\u548c\u5f3a\u76f4\u6027\u808c\u8089\u8425\u517b\u4e0d\u826f\u75c7\uff09\u7684\u5019\u9009\u836f\u7269\u3002\u5c0f\u5206\u5b50\u5316\u5408\u7269AQAMAN\u4fbf\u662f\u7531Zimmerman\u6559\u6388\u7684\u56e2\u961f\u751f\u4ea7\uff0c\u539f\u5b9a\u7528\u4e8e\u6cbb\u7597\u5f3a\u76f4\u6027\u808c\u8089\u8425\u517b\u4e0d\u826f\u75c7\uff08\u4e00\u7ec4\u808c\u8089\u840e\u7f29\uff0f\u9000\u5316\u75be\u75c5\uff09\u3002\u9648\u6559\u6388\u7684\u56e2\u961f\u5076\u7136\u53d1\u73b0AQAMAN\u5bf9polyQ\u75be\u75c5\u4ea6\u6709\u6f5c\u5728\u7597\u6548\u3002PolyQ\u75be\u75c5\u662f\u4e00\u7ec4\u7531\u86cb\u767d\u8d28\u805a\u5408\u4f53\u5f15\u53d1\u7684\u795e\u7ecf\u9000\u884c\u6027\u75be\u75c5\uff0c\u800cAQAMAN\u80fd\u5e72\u6270polyQ\u86cb\u767d\u8d28\u805a\u5408\u4f53\u5f62\u6210\uff0c\u5e76\u4fc3\u4f7f\u5df2\u5f62\u6210\u7684\u805a\u5408\u4f53\u5206\u89e3\u3002\u9648\u6559\u6388\u7684\u56e2\u961f\u76ee\u524d\u6b63\u5728\u5bfb\u6c42\u836f\u5382\u4e3a\u5408\u4f5c\u4f19\u4f34\uff0c\u4ee5\u8fdb\u4e00\u6b65\u6539\u5584AQAMAN\u7684\u836f\u6027\u3002<\/p><p>\u9648\u6559\u6388\u8bf4\uff1a\u300c\u9519\u8bef\u6298\u53e0\u548c\u805a\u96c6\u7684\u86cb\u767d\u8d28\u4e0e\u591a\u79cd\u4eba\u7c7b\u75be\u75c5\u5bc6\u5207\u76f8\u5173\u3002\u81ea1999\u5e74\u4ee5\u6765\uff0c\u6211\u4e00\u76f4\u7814\u7a76polyQ\u86cb\u767d\u805a\u5408\u4f53\u5982\u4f55\u5bfc\u81f4\u795e\u7ecf\u7ec6\u80de\u9000\u5316\uff0c\u5e76\u8bd5\u56fe\u4ee5\u9057\u4f20\u7b56\u7565\u6765\u5e72\u9884\u6709\u6bd2polyQ\u805a\u5408\u4f53\u7684\u5f62\u6210\u3002\u81ea2012\u5e74\u8d77\uff0c\u6211\u4e0eZimmerman\u6559\u6388\u5408\u4f5c\uff0c\u4f7f\u7528\u679c\u8747<em>Drosophila<\/em>\u4f5c\u4e3a\u836f\u7269\u7b5b\u9009\u6a21\u578b\uff0c\u7528\u6765\u6d4b\u8bd5\u53ca\u8bc4\u4f30\u4e0d\u540c\u7684\u5c0f\u5206\u5b50\u5316\u5408\u7269\u5bf9\u533b\u6cbb\u5f3a\u76f4\u6027\u808c\u8089\u8425\u517b\u4e0d\u826f\u75c7\u7684\u6548\u679c\u3002\u540e\u6765\u57282016\u5e74\uff0c\u6211\u4e0e\u7ba1\u8fdb\u6559\u6388\uff08\u4e2d\u5927\u751f\u547d\u79d1\u5b66\u5b66\u9662\uff09\u5408\u4f5c\uff0c\u4f7f\u7528\u679c\u8747\u7684\u795e\u7ecf\u808c\u8089\u63a5\u5934\u6765\u7814\u7a76\u5f3a\u76f4\u6027\u808c\u8089\u8425\u517b\u4e0d\u826f\u75c7\u7684\u75be\u75c5\u673a\u5236\u3002AQAMAN\u662f\u4f17\u591a\u57fa\u4e8e\u53cc\u8112\u7684\u6291\u5236\u5242\u4e4b\u4e00\uff0c\u539f\u672c\u662f\u7528\u6765\u6291\u5236\u5f3a\u76f4\u6027\u808c\u8089\u8425\u517b\u4e0d\u826f\u75c7\u4e2d\u7684\u6838\u7cd6\u6838\u9178&ndash;\u86cb\u767d\u590d\u5408\u7269\u3002\u4f46\u51fa\u4e4e\u6211\u4eec\u9884\u671f\uff0cAQAMAN\u7adf\u7136\u5177\u6709\u5e72\u6270\u6709\u6bd2\u86cb\u767d\u8d28\u805a\u96c6\u7684\u80fd\u529b\u3002\u6211\u4eec\u5e0c\u671b\u8fdb\u4e00\u6b65\u7814\u53d1AQAMAN\u4f5c\u4e34\u5e8a\u6cbb\u7597\u7528\u9014\uff0c\u4e3apolyQ\u75be\u75c5\u60a3\u8005\u5e26\u6765\u5e0c\u671b\u3002\u300d<\/p><p>\u662f\u9879\u7814\u7a76\u83b7\u4e2d\u5927\u6821\u957f\u5907\u7528\u57fa\u91d1\u3001\u4e2d\u5927\u5415\u5fd7\u548c\u521b\u65b0\u533b\u5b66\u7814\u7a76\u6240\u3001\u4e2d\u5927\u8521\u6c38\u4e1a\u8111\u795e\u7ecf\u79d1\u5b66\u4e2d\u5fc3\u3001\u88d8\u69ce\u57fa\u91d1\u4f1a\u3001\u7f8e\u56fd\u56fd\u5bb6\u536b\u751f\u7814\u7a76\u9662\uff0c\u4ee5\u53ca\u9999\u6e2f\u5c0f\u8111\u840e\u7f29\u75c7\u534f\u4f1a\u7684\u6350\u6b3e\u8d44\u52a9\u3002<\/p><p><strong>\u6539\u826f\u578b\u591a\u80bd\u6291\u5236\u5242\u80fd\u5bf9\u6297\u795e\u7ecf\u9000\u5316\u75be\u75c5\u7684<\/strong><strong> RNA<\/strong><strong>\u6bd2\u6027<\/strong><\/p><p>2016\u5e74\uff0c\u9648\u6559\u6388\u4e0e\u4e2d\u5927\u751f\u547d\u79d1\u5b66\u5b66\u9662\u6556\u5fd7\u797a\u6559\u6388\u5408\u4f5c\uff0c\u81f4\u529b\u5f00\u53d1\u4e00\u79cd\u65b0\u578b\u591a\u80bd\u6291\u5236\u5242\uff0c\u7528\u4e8e\u62b5\u6297polyQ\u75be\u75c5\u7684CAG RNA\u6bd2\u6027\u3002\u6556\u6559\u6388\u662f\u4e00\u4f4d\u7ed3\u6784\u751f\u7269\u5b66\u5bb6\u548c\u8d44\u6df1\u7684\u836f\u7269\u7814\u53d1\u4e13\u5bb6\u3002\u56e2\u961f\u6700\u8fd1\u53d1\u73b0\u4e86\u4e00\u79cd\u753121\u4e2a\u6c28\u57fa\u9178\u7ec4\u6210\u7684\u591a\u80bd\u5206\u5b50\uff0c\u4f5c\u4e3a\u7528\u4e8e\u795e\u7ecf\u9000\u5316\u6027\u75be\u75c5\u7684\u6539\u826f\u578b\u591a\u80bd\u6291\u5236\u5242\uff0c\u5e76\u547d\u540d\u4e3aBIND\u3002\u8fd9\u79cd\u6291\u5236\u5242\u80fd\u9488\u5bf9polyQ\u75be\u75c5\u548cC9orf72-\u76f8\u5173\u7684\u808c\u840e\u7f29\u6027\u810a\u9ad3\u4fa7\u7d22\u786c\u5316\u75c7\uff08\u53c8\u540d\u6e10\u51bb\u4eba\u75c7\uff09\/ 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FTD\u4e2d\u7684RNA\u6bd2\u6027\u5219\u7531GGGGCC\u91cd\u590d\u6269\u589e\u5f15\u8d77\u3002GGGGCC\u662f\u5728\u4eba\u7c7b\u57fa\u56e0\u7ec4\u4e2d\u7684\u4e00\u79cd\u516d\u6838\u82f7\u9178\u91cd\u590dDNA\u5e8f\u5217\uff0c\u4e0d\u53d7\u63a7\u5236\u7684GGGGCC\u91cd\u590d\u6269\u589e\u4f1a\u5bfc\u81f4C9ALS \/ FTD\u7f55\u89c1\u75be\u75c5\u3002\u5c3d\u7ba1polyQ\u548cC9ALS \/ 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