{"id":28908,"date":"2022-10-20T00:18:06","date_gmt":"2022-10-19T16:18:06","guid":{"rendered":"https:\/newsletter.sinica.edu.tw\/?p=28908"},"modified":"2022-10-20T00:37:33","modified_gmt":"2022-10-19T16:37:33","slug":"%e3%80%90%e5%b0%88%e6%ac%84%e3%80%91%e4%bb%80%e9%ba%bc%ef%bc%9f%e4%b9%9f%e6%9c%89%e5%a3%9e%e7%9a%84%e8%9b%8b%e7%99%bd%e8%b3%aa%ef%bc%9f-%e6%b7%ba%e8%ab%87%e8%9b%8b%e7%99%bd%e8%b3%aa","status":"publish","type":"post","link":"https:\/newsletter.sinica.edu.tw\/28908\/","title":{"rendered":"\u3010\u5c08\u6b04\u3011\u4ec0\u9ebc\uff1f\u4e5f\u6709\u58de\u7684\u86cb\u767d\u8cea\uff1f\u2014\u2014\u6dfa\u8ac7\u86cb\u767d\u8cea\u932f\u8aa4\u647a\u758a\u8207\u795e\u7d93\u9000\u5316\u75be\u75c5"},"content":{"rendered":"

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\u7136\u800c\u4eca\u5e74\u9802\u5c16\u7684\u5b78\u8853\u671f\u520a Science<\/em> \u520a\u767b\u4e00\u7bc7\u5075\u67e5\u5831\u5c0e\uff0c\u8cea\u7591\u767c\u8868\u5728 2006 \u5e74 Nature<\/em> \u7684\u4e00\u7bc7\u91cd\u78c5\u8ad6\u6587\u9020\u5047\uff0c\u9019\u4ee4\u570b\u969b\u793e\u6703\u611f\u5230\u9707\u9a5a\u3002\u5176\u4e2d\u7684\u8cea\u7591\u9ede\u5728\u65bc\u963f\u8332\u6d77\u9ed8\u75c7\uff08Alzheimer’s disease, AD\uff0c\u4fd7\u7a31\u8001\u5e74\u5931\u667a\u75c7\uff09\u7684\u75c5\u7406\u86cb\u767d\u2014\u2014\u4e59\u578b\u985e\u6fb1\u7c89\u86cb\u767d\uff08Amyloid \u03b2 , A\u03b2\uff09\u7684\u5be6\u9a57\u6578\u64da\u3002\u518d\u52a0\u4e0a 2021 \u5e74\u7f8e\u570b\u98df\u54c1\u85e5\u7269\u7ba1\u7406\u5c40\u9996\u6b21\u901a\u904e\u767e\u5065\uff08Biogen\uff09\u85e5\u5ee0\u7684 A\u03b2 \u6297\u9ad4\u85e5\u7269aducanumab\uff0c\u56e0\u70ba\u5176\u6210\u6548\u4e0d\u5f35\u800c\u98fd\u53d7\u8cea\u7591\u3002\u9019\u7686\u4f7f\u5f97 A\u03b2 \u6210\u70ba\u773e\u4eba\u8cea\u7591\u7684\u7bad\u9776\uff0c\u61f7\u7591\u5b83\u662f\u5426\u771f\u7684\u662f\u963f\u8332\u6d77\u9ed8\u75c7\u7684\u539f\u5147\u3002<\/p>\n

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\u5c08\u4e00\u6297\u9ad4\u4f86\u64ca\u9000\u65b0\u578b TDP-43 \u86cb\u767d\u8cea\u75be\u75c5\u4e86\uff01<\/strong><\/p>\n

\u5f8c\u4f86\u6211\u5011\u4e5f\u6f38\u6f38\u5c07\u7814\u7a76\u5ef6\u4f38\u5230 TDP-43 \u86cb\u767d\u8cea\u75be\u75c5\u4e0a\u3002TDP-43 \u86cb\u767d\u662f\u65bc 2006 \u5e74\u5728\u984d\u9873\u8449\u5931\u61b6\u75c7\uff08FTD\uff09\u53ca\u6f38\u51cd\u4eba\u75c7\uff08ALS\uff09\u4e2d\u88ab\u767c\u73fe\u7684\u6c89\u7a4d\u7269\u3002\u6211\u5011\u9996\u5148\u5c07\u4eba\u985e\u7684 TDP-43 \u5168\u9577\u86cb\u767d\u7d14\u5316\u51fa\u4f86\uff0c\u767c\u73fe\u5b83\u6703\u5feb\u901f\u5730\u805a\u96c6\u6210\u5177\u6709\u795e\u7d93\u6bd2\u6027\u7684\u7403\u72c0\u5be1\u805a\u9ad4 6<\/sup>\u3002\u66f4\u9032\u4e00\u6b65\u88fd\u4f5c\u51fa\u80fd\u5c08\u4e00\u8fa8\u8a8d TDP-43 \u7403\u72c0\u5be1\u805a\u9ad4\u7684\u5c08\u4e00\u6297\u9ad4\uff0c\u5176\u4e0d\u6703\u8fa8\u8b58\u751f\u7406\u4e0a\u5177\u6709\u6b63\u5e38\u529f\u80fd\u7684 TDP-43\uff0c\u671f\u8a31\u5b83\u80fd\u5920\u6210\u70ba\u4e00\u500b\u6297\u9ad4\u65b0\u85e5\u3002\u9019\u500b\u5c08\u4e00\u6297\u9ad4\u53ea\u6253\u64ca\u932f\u8aa4\u647a\u758a\u7684 TDP-43 \u58de\u86cb\uff0c\u800c\u4e0d\u53bb\u653b\u64ca\u6b63\u5e38\u529f\u80fd\u7684\u597d TDP-43 \u86cb\u767d\u3002\u807d\u8d77\u4f86\u662f\u4e0d\u662f\u5f88\u68d2\u5462\uff1f<\/p>\n

\u76ee\u524d\u6211\u5011\u5df2\u751f\u7522\u4e86\u5177\u7d50\u69cb\u5c08\u4e00\u6027\u7684\u5c0f\u9f20\u55ae\u682a\u6297\u9ad4\uff0c\u6bcf\u9031\u975c\u8108\u6ce8\u5c04\u5230 ALS \u5c0f\u9f20\u6a21\u578b\u4e2d\uff0c\u518d\u8b93\u5c0f\u9f20\u8dd1\u5065\u8eab\u6efe\u8f2a\uff0c\u767c\u73fe\uff1a\u76f8\u8f03\u65bc\u6ce8\u5c04\u63a7\u5236\u7d44\u6297\u9ad4\u7684\u5c0f\u9f20\uff0c\u6ce8\u5c04\u4e86\u9019\u500b\u6297\u9ad4\u7684\u5c0f\u9f20\u8dd1\u5f97\u6bd4\u8f03\u70ba\u6301\u4e45\uff0c\u5176\u5f8c\u80a2\u5f35\u529b\u4e5f\u7dad\u6301\u6b63\u5e38\uff0c\u904b\u52d5\u795e\u7d93\u5143\u7684\u6578\u91cf\u4e5f\u986f\u8457\u5730\u6bd4\u8f03\u591a\uff0c\u56e0\u6b64\u6211\u5011\u5728\u5c0f\u9f20\u9ad4\u5167\u8b49\u660e\u4e86\u9019\u500b\u6297\u9ad4\u7684\u6cbb\u7642\u529f\u6548\u3002<\/p>\n

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\u25b2\u85c9\u7531\u5c08\u4e00\u6297\u9ad4\uff08\u7da0\u8272\u7684 Y \u5b57\u578b\uff09\u53ef\u4ee5\u514d\u75ab\u67d3\u8272\u51fa\u75c5\u4eba\u8166\u7d44\u7e54\u4e2d\u7684\u75c5\u7406\u86cb\u767d\uff08\u4e2d\u5716\uff09\uff0c\u4e5f\u53ef\u4ee5\u514d\u75ab\u6c89\u6fb1\u51fa\u9019\u500b\u5143\u51f6\uff08\u5de6\u5716\uff0c\u96fb\u5b50\u986f\u5fae\u93e1\u5716\uff096<\/sup>\u3002<\/p><\/div>\n

\u95dc\u9375\u7684\u7b2c\u4e09\u8005\u51fa\u73fe\u4e86\uff01<\/strong><\/p>\n

\u963f\u8332\u6d77\u9ed8\u75c7\u4e2d\u9664\u4e86\u5df2\u77e5\u7684 A\u03b2 \u548c Tau \u86cb\u767d\u5806\u7a4d\uff0c\u8fd1\u5e74\u4f86\u5728\u8a31\u591a\u963f\u8332\u6d77\u9ed8\u75c7\u60a3\u8005\u8166\u4e2d\u767c\u73fe\u4e86\u7b2c\u4e09\u8005\uff01\u5b83\u7adf\u7136\u662f TDP-43 \u86cb\u767d\u6c89\u7a4d\u7269\u2026\u2026<\/p>\n

TDP-43 \u86cb\u767d\u4e0d\u662f\u50c5\u88ab\u767c\u73fe\u5728 95%ALS \u548c 50% \u984d\u9873\u8449\u5931\u667a\u75c7\u75c5\u4eba\u75c5\u7406\u4e2d\u6c89\u7a4d\u7269\uff0c\u73fe\u5728\u5c45\u7136\u4e5f\u8de8\u754c\u5230\u4e86\u963f\u8332\u6d77\u9ed8\u75c7\uff1f\u7684\u78ba\uff0c\u570b\u5916\u963f\u8332\u6d77\u9ed8\u75c7\u75c5\u7406\u4e2d\u5fc3\u5206\u6790\u9ad8\u9054\u4e09\u767e\u591a\u4f4d\u904e\u4e16\u5f8c\u6350\u8166\u7684\u75c5\u4eba\uff0c\u5176\u75c5\u7a0b\u6578\u64da\u53ca\u8166\u7d44\u7e54\u75c5\u7406\u986f\u793a\uff1a\u9ad8\u9054 57% \u5927\u8166\u5e36\u6709 TDP-43 \u86cb\u767d\u6c89\u7a4d\u7269\u7684\u75c5\u4eba\u51fa\u73fe\u66f4\u5feb\u901f\u7684\u75c5\u7a0b\u548c\u66f4\u5927\u898f\u6a21\u7684\u8166\u840e\u7e2e\u3002<\/p>\n

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\u5176\u5be6\uff0c\u6211\u5011\u5148\u524d\u5c31\u89c0\u5bdf\u5230\u5168\u9577 TDP-43 \u5be1\u805a\u9ad4\u6703\u5e72\u64fe A\u03b2 \u7684\u7e96\u7dad\u5316\u904e\u7a0b\u3002\u6211\u5011\u63a5\u7e8c\u8457\u6df1\u5165\u7814\u7a76 TDP-43 \u5728\u963f\u8332\u6d77\u9ed8\u75c7\u4e2d\u7684\u89d2\u8272 7<\/sup>\u3002\u6211\u5011\u767c\u73fe TDP-43 \u53ef\u4ee5\u5728 A\u03b2 \u805a\u96c6\u904e\u7a0b\u7684\u521d\u671f\u548c\u4e2d\u671f\u900f\u904e\u4ea4\u4e92\u4f5c\u7528\u5f71\u97ff\u4e26\u6291\u5236 A\u03b2 \u9577\u6210\u7e96\u7dad\uff0c\u6b64\u4f5c\u7528\u4f7f\u5f97\u904e\u7a0b\u4e2d\u7684 A\u03b2 \u5be1\u805a\u9ad4\u4e5f\u589e\u52a0\u4e86\u3002<\/p>\n

\u5728\u5c0f\u9f20\u884c\u70ba\u5be6\u9a57\u4e2d\uff0c\u6211\u5011\u6ce8\u5c04 TDP-43 \u8a98\u5c0e\u7684 A\u03b2 \u5230\u6b63\u5e38\u5c0f\u9f20\u8166\u4e2d\uff0c\u5c0f\u9f20\u6703\u6709\u986f\u8457\u60e1\u5316\u7684\u7a7a\u9593\u8a18\u61b6\u640d\u50b7\u3002\u800c\u4f7f\u7528\u57fa\u56e0\u8f49\u6b96\u7684\u963f\u8332\u6d77\u9ed8\u75c7\u6a21\u5f0f\u9f20\uff0c\u6ce8\u5c04 TDP-43 \u4e5f\u6709\u4e00\u6a23\u7684\u554f\u984c\uff0c\u4e26\u4e14\u5f15\u8d77\u5927\u8166\u4e2d\u7684\u767c\u708e\u53cd\u61c9\u3002\u6211\u5011\u4e5f\u78ba\u8a8d TDP-43 \u8207 A\u03b2 \u6709\u76f8\u4e92\u4f5c\u7528\uff0c\u4e26\u52a0\u5287\u4e86\u963f\u8332\u6d77\u9ed8\u75c7\u75c5\u5fb5\u3002\u66f4\u91cd\u8981\u7684\u662f\uff0c\u6211\u5011\u767c\u73fe TDP-43 \u5be1\u805a\u9ad4\u5728\u963f\u8332\u6d77\u9ed8\u75c7\u60a3\u8005\u5927\u8166\u7684\u795e\u7d93\u7d30\u80de\u5167\u8207 A\u03b2 \u5ea7\u843d\u65bc\u540c\u4e00\u500b\u4f4d\u7f6e\u3002\u56e0\u6b64\uff0c\u6211\u5011\u7684\u7814\u7a76\u63d0\u4f9b\u4e86 TDP-43 \u9019\u500b\u7b2c\u4e09\u8005\uff0c\u900f\u904e\u76f8\u4e92\u4f5c\u7528\u6291\u5236\u4e3b\u4e8b\u8005 A\u03b2 \u7684\u7e96\u7dad\u5316\uff0c\u4e26\u52a0\u5287\u4e86 AD \u75c5\u5fb5\u7684\u5206\u5b50\u6a5f\u5236\u3002<\/p>\n

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\u25b2 TDP-43 \u5be1\u805a\u9ad4\u60e1\u5316\u963f\u8332\u6d77\u9ed8\u75c7\u75c5\u5fb5\u3002 TDP-43 \u5be1\u805a\u9ad4\u6291\u5236 A\u03b2 \u7e96\u7dad\u53ca\u8a98\u767c A\u03b2 \u5be1\u805a\u9ad4\u5f62\u6210\uff08\u5de6\u5716\u4e00\u4e8c\uff0c\u96fb\u5b50\u986f\u5fae\u93e1\u5716\uff09\u3002TDP-43\u5be1\u805a\u9ad4\u548c A\u03b2 \u5ea7\u843d\u65bc\u5728\u963f\u8332\u6d77\u9ed8\u75c7\u5927\u8166\u7684\u795e\u7d93\u7d30\u80de\u5167\uff08\u4e2d\u5716\uff09\u3002TDP-43 \u5be1\u805a\u9ad4\u5f15\u8d77\u767c\u708e\u53cd\u61c9\uff08\u53f3\u5716\uff09\u3002<\/p><\/div>\n

\u672a\u4f86\u5c55\u671b<\/strong><\/p>\n

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\u53c3\u8003\u6587\u737b<\/strong><\/p>\n

1.Chen, Y. R.; Glabe, C. G., Distinct early folding and aggregation properties of Alzheimer amyloid-beta peptides Abeta40 and Abeta42: stable trimer or tetramer formation by Abeta42. J Biol Chem<\/em> 2006, 281<\/em>\uff0834\uff09, 24414-22.
\n2.Ni, C. L.; Shi, H. P.; Yu, H. M.; Chang, Y. C.; Chen, Y. R., Folding stability of amyloid-beta 40 monomer is an important determinant of the nucleation kinetics in fibrillization. FASEB J<\/em> 2011, 25<\/em>\uff084\uff09, 1390-401.
\n3.Chen, W. T.; Liao, Y. H.; Yu, H. M.; Cheng, I. H.; Chen, Y. R., Distinct effects of Zn2+, Cu2+, Fe3+, and Al3+ on amyloid-beta stability, oligomerization, and aggregation: amyloid-beta destabilization promotes annular protofibril formation. J Biol Chem<\/em> 2011, 286<\/em>\uff0811\uff09, 9646-56.
\n4.Lee, M. C.; Yu, W. C.; Shih, Y. H.; Chen, C. Y.; Guo, Z. H.; Huang, S. J.; Chan, J. C. C.; Chen, Y. R., Zinc ion rapidly induces toxic, off-pathway amyloid-beta oligomers distinct from amyloid-beta derived diffusible ligands in Alzheimer’s disease. Scientific reports<\/em> 2018, 8<\/em>\uff081\uff09, 4772.
\n5.Liao, Y. H.; Chang, Y. J.; Yoshiike, Y.; Chang, Y. C.; Chen, Y. R., Negatively charged gold nanoparticles inhibit Alzheimer’s amyloid-beta fibrillization, induce fibril dissociation, and mitigate neurotoxicity. Small<\/em> 2012, 8<\/em>\uff0823\uff09, 3631-9.
\n6.Fang, Y. S.; Tsai, K. J.; Chang, Y. J.; Kao, P.; Woods, R.; Kuo, P. H.; Wu, C. C.; Liao, J. Y.; Chou, S. C.; Lin, V.; Jin, L. W.; Yuan, H. S.; Cheng, I. H.; Tu, P. H.; Chen, Y. R., Full-length TDP-43 forms toxic amyloid oligomers that are present in frontotemporal lobar dementia-TDP patients. Nat Commun<\/em> 2014, 5<\/em>, 4824.
\n7.Shih, Y. H.; Tu, L. H.; Chang, T. Y.; Ganesan, K.; Chang, W. W.; Chang, P. S.; Fang, Y. S.; Lin, Y. T.; Jin, L. W.; Chen, Y. R., TDP-43 interacts with amyloid-beta, inhibits fibrillization, and worsens pathology in a model of Alzheimer’s disease. Nat Commun<\/em> 2020, 11<\/em>\uff081\uff09, 5950.<\/p>\n","protected":false},"excerpt":{"rendered":"

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