利用籠化TDP-43胜肽片段觀察光引導類澱粉纖維形成之過程;Monitoring the light-induced amyliodogenesis with caged TDP-43 peptides

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题名:	利用籠化TDP-43胜肽片段觀察光引導類澱粉纖維形成之過程;Monitoring the light-induced amyliodogenesis with caged TDP-43 peptides
作者:	趙書漢;Chao,Shu-Han
贡献者:	化學學系
关键词:	胜肽;TDP-43
日期:	2015-07-20
上传时间:	2015-09-23 10:44:55 (UTC+8)
出版者:	國立中央大學
摘要:	透過實驗室先前的研究成果，我們發現TDP-43 蛋白質的胜肽片段，其具有快速聚集化形成類澱粉纖維之特性，利用此片段快速聚集化之特性，本研究在光解前後此胜肽聚集化形成類澱粉纖維之速度會有極大差異，因此在結構上的轉變也會相差許多，而後經由時間培養使用圓二色光譜儀鑑別其照光前後之二級結構；穿透式電子顯微鏡觀察其照光前後構形的變化；可見光紫外光光譜儀偵測其照光前後混濁度之差異。於活細胞實驗中，先將此胜肽片段合成上螢光基團後，再加入細胞中進行觀察。此光化學胜肽可以順利進入細胞內與加入 AICAR 後mislocalization 的TDP-43 蛋白質相互作用。透過足夠UV 光的照射，失去抑制聚集化形成類澱粉纖維的胜肽，將與細胞質內的 TDP-43 蛋白質互相作用，並經由引晶效應（seeding effect）使TDP-43 蛋白質聚集化而形成aggregates。此光化學胜肽極有潛力能成為一個 ALS 在疾病上的模型（disease model），且可以期待它在其它神經退化性疾病中的廣泛討論與應用。;Photolytic device has been used widely in the controlled release of chemicals. Previously we have identified the core sequence of TDP-43’s C terminus and characterized its rapid aggregation and amyloidogenesis. In this study, we synthesized a photochemically inducible peptide. Provided that the amyloidogenicity of the peptide would be only activated upon UV-initiated photocleavage. From 1) the ultrastructural changes observed under a transmission electron microscope (TEM), 2) the secondary structure alteration revealed by circular dichroism (CD), and 3) the turbidity assessed by UV–visible spectrophotometer, the significant changes of the peptide after UV illumination were reported. In addition to the in vitro characterizations, the fluorophore was conjugated to the peptide to learn its dynamics in neuronal cells since it also confers cell membrane permeability. Of note, only UV-mediated release of this peptide is capable of triggering cytosolic TDP-43 to form amyloid fiber. Taken these together, this photochemically inducible peptide could serve as a simple but powerful disease model of ALS and its further application on neurodegenerative diseases is highly expected as well.
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