{"id":648,"date":"2017-03-14T11:50:30","date_gmt":"2017-03-14T02:50:30","guid":{"rendered":"http:\/\/www2.med.osaka-u.ac.jp\/wwwmed\/eng\/activities\/results\/2007year\/nagai-yoshitaka"},"modified":"2017-04-28T15:30:16","modified_gmt":"2017-04-28T06:30:16","slug":"article04","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2007year\/article04","title":{"rendered":"NAGAI Yoshitaka \u226aClinical Genetics\u226b <span>\u201cA toxic monomeric conformer of the polyglutamine protein.\u201d<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li> <a href=\"http:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2007year\/article04\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><!-- \n\n<h1>\u6c38\u4e95 \u7fa9\u9686 \u226a\u81e8\u5e8a\u907a\u4f1d\u5b66\u226b<\/h1>\n\n --><\/p>\n<p class=\"figure\"><a href=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2007\/nagai200704.jpeg\" target=\"_blank\" class=\"zoom\"><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2007\/nagai200704.jpeg\" alt=\"\" height=\"124\" width=\"200\" \/><br \/>\n  <span class=\"click\">Click to enlarge<\/span><\/a><\/p>\n<p>2007-4<br \/>\n  <span class=\"lineFrame\">Publish<\/span> Nature Struct. Mol. Biol. 14: 332-340 (2007) <\/p>\n<p><!-- \n\n<h3>\u30dd\u30ea\u30b0\u30eb\u30bf\u30df\u30f3\u86cb\u767d\u8cea\u306e\u6bd2\u6027\u69cb\u9020\u4f53\u306f\u03b2\u30b7\u30fc\u30c8\u30e2\u30ce\u30de\u30fc\u3067\u3042\u308b<\/h3>\n\n\n\n\n<p>\u8981\u65e8\uff1a\u8fd1\u5e74\u3001\u30a2\u30eb\u30c4\u30cf\u30a4\u30de\u30fc\u75c5\u3001\u30d1\u30fc\u30ad\u30f3\u30bd\u30f3\u75c5\u3001\u30dd\u30ea\u30b0\u30eb\u30bf\u30df\u30f3\u75c5\u306a\u3069\u306e\u591a\u304f\u306e\u795e\u7d4c\u5909\u6027\u75be\u60a3\u3067\u306f\u3001\u7570\u5e38\u86cb\u767d\u8cea  \u304c\u795e\u7d4c\u7d30\u80de\u5185\u5916\u306b\u51dd\u96c6\u30fb\u84c4\u7a4d\u3057\u3066\u5171\u901a\u306b\u795e\u7d4c\u5909\u6027\u3092\u5f15\u304d\u8d77\u3053\u3059\u3068\u8003\u3048\u3089\u308c\u3066\u3044\u308b\u304c\u3001\u3053\u306e\u904e\u7a0b\u3067\u795e\u7d4c\u6bd2\u6027\u3092\u767a\u63ee\u3059\u308b\u86cb\u767d\u8cea\u306e\u69cb\u9020\u5909\u5316\u306b\u3064\u3044\u3066\u306f\u672a\u89e3\u660e\u3067\u3042\u3063  \u305f\u3002\u672c\u7814\u7a76\u3067\u306f\u30dd\u30ea\u30b0\u30eb\u30bf\u30df\u30f3\u86cb\u767d\u8cea\u306e\u751f\u5316\u5b66\u7684\u30fb\u69cb\u9020\u751f\u7269\u5b66\u7684\u89e3\u6790\u3092\u884c\u3044\u3001\u7570\u5e38\u4f38\u9577\u30dd\u30ea\u30b0\u30eb\u30bf\u30df\u30f3\u86cb\u767d\u8cea\u306f\u51dd\u96c6\u3059\u308b\u524d\u306b\u30e2\u30ce\u30de\u30fc\u306e\u72b6\u614b\u3067\u03b2\u30b7\u30fc\u30c8\u69cb\u9020\u3078\u306e  \u7570\u5e38\u30b3\u30f3\u30d5\u30a9\u30e1\u30fc\u30b7\u30e7\u30f3\u5909\u79fb\u3092\u7372\u5f97\u3057\u3066\u3001\u30a2\u30df\u30ed\u30a4\u30c9\u7dda\u7dad\u72b6\u51dd\u96c6\u4f53\u3092\u5f62\u6210\u3059\u308b\u3053\u3068\u3092\u660e\u3089\u304b\u306b\u3057\u305f\u3002\u305d\u3057\u3066\u3001\u03b2\u30b7\u30fc\u30c8\u5909\u79fb\u3057\u305f\u30dd\u30ea\u30b0\u30eb\u30bf\u30df\u30f3\u86cb\u767d\u8cea\u30e2\u30ce\u30de\u30fc\u304c  \u7d30\u80de\u6bd2\u6027\u3092\u767a\u63ee\u3059\u308b\u3053\u3068\u3092\u521d\u3081\u3066\u660e\u3089\u304b\u306b\u3057\u305f\u3002\u3055\u3089\u306b\u3001\u7570\u5e38\u4f38\u9577\u30dd\u30ea\u30b0\u30eb\u30bf\u30df\u30f3\u9396\u7d50\u5408\u30da\u30d7\u30c1\u30c9QBP1\u304c\u3053\u306e\u6bd2\u6027\u03b2\u30b7\u30fc\u30c8\u5909\u79fb\u3092\u963b\u5bb3\u3057\u3066\u3001\u795e\u7d4c\u5909\u6027\u3092\u6291\u5236  \u3059\u308b\u3053\u3068\u3092\u898b\u51fa\u3057\u305f\u3002\u4ee5\u4e0a\u306e\u7d50\u679c\u304b\u3089\u3001\u30dd\u30ea\u30b0\u30eb\u30bf\u30df\u30f3\u75c5\u306e\u307f\u306a\u3089\u305a\u4ed6\u306e\u795e\u7d4c\u5909\u6027\u75be\u60a3\u306b\u304a\u3044\u3066\u3082\u3001\u7570\u5e38\u86cb\u767d\u8cea\u306e\u03b2\u30b7\u30fc\u30c8\u5909\u79fb\u304c\u6cbb\u7642\u6a19\u7684\u3068\u306a\u308b\u3068\u8003\u3048\u3089\u308c\u3001\u6cbb  \u7642\u85ac\u958b\u767a\u3078\u306e\u9053\u7b4b\u3092\u793a\u3057\u305f\u3002<\/p>\n\n --><\/p>\n<p> Polyglutamine (polyQ) diseases are   classified as conformational neurodegenerative diseases, like Alzheimer   and Parkinson diseases, and they are caused by proteins with an   abnormally expanded polyQ stretch. However, conformational changes of   the expanded polyQ protein and the toxic conformers formed during   aggregation have remained poorly understood despite their important role   in pathogenesis. Here we show that a \u03b2-sheet conformational transition   of the expanded polyQ protein monomer precedes its assembly into   \u03b2-sheet-rich amyloid-like fibrils. Microinjection of the various polyQ   protein conformers into cultured cells revealed that the soluble \u03b2-sheet   monomer causes cytotoxicity. The polyQ-binding peptide QBP1 prevents   the toxic \u03b2-sheet conformational transition of the expanded polyQ   protein monomer. We conclude that the toxic conformational transition,   and not simply the aggregation process itself, is a therapeutic target   for polyQ diseases and possibly for conformational diseases in general.<\/p>\n<p class=\"mt25\"><span class=\"lineFrame\">URL<\/span> <a href=\"http:\/\/www.med.osaka-u.ac.jp\/pub\/clgene\/www\/menu.html\" target=\"_blank\">http:\/\/www.med.osaka-u.ac.jp\/pub\/clgene\/www\/menu.html<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Click to enlarge 2007-4 Publish Nature Struct. Mol. Biol. 14: 332-340 (2007) Polyglutamine (p [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":1818,"parent":464,"menu_order":171,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/648"}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=648"}],"version-history":[{"count":6,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/648\/revisions"}],"predecessor-version":[{"id":2367,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/648\/revisions\/2367"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/464"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/1818"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=648"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}