董晓燕, 齐凤娟, 张焕, 赵彦娇
AuthorsHTML:董晓燕, 齐凤娟, 张焕, 赵彦娇
AuthorsListE:Dong Xiaoyan, Qi Fengjuan, Zhang Huan, Zhao Yanjiao
AuthorsHTMLE:Dong Xiaoyan, Qi Fengjuan, Zhang Huan, Zhao Yanjiao
Unit:天津大学化工学院，天津 300354
Unit_EngLish:School of Chemical Engineering and Technology, Tianjin University, Tianjin 300354, China
Abstract_Chinese:淀粉样β蛋白(amyloid β-protein, Aβ)的二次成核机制认为Aβ聚集体可作为种子加速Aβ聚集．而Cu²⁺与Aβ结合也会加剧Aβ聚集, 因此了解Cu²⁺诱导的Aβ种子对Aβ二次成核的影响具有重要意义．本文考察了不同浓度Cu²⁺诱导的Aβ₄₀种子对Aβ₄₀聚集过程、聚集体形貌、二级结构以及细胞毒性的影响．结果表明, 随着Cu²⁺浓度增加, Aβ₄₀种子形貌由纤维状转变为球形．并且, 两种形貌的Aβ₄₀种子均可促进Aβ₄₀二次成核并形成富含β-折叠结构的纤维状聚集体．其中, 纤维状种子比球形种子的促进作用更强并具有浓度依赖效应．值得注意的是, 两种形貌的种子诱导的Aβ₄₀聚集体细胞毒性具有明显差异．对比发现：球形种子诱导的Aβ₄₀聚集体比纤维状种子诱导的聚集体毒性显著加剧．本文明确了Cu²⁺诱导产生的种子对Aβ聚集的促进作用, 可为开发有效的Aβ聚集抑制剂提供理论依据．
Abstract_English:The secondary nucleation mechanism of amyloid β-protein(Aβ)suggests that the pre-formed Aβ aggregates promote Aβ fibrillation as nucleation seeds. The binding of Cu²⁺ to Aβ also accelerates Aβ aggregation. So，it is of great significance to study the effect of Aβ seeds induced by Cu²⁺ on Aβ secondary nucleation. The effects of Aβ₄₀ seeds induced by different concentrations of Cu²⁺ on Aβ₄₀ aggregation，morphology，secondary structure and cytotoxicity were investigated. The results indicate that with increasing concentration of Cu²⁺，the morphology of Aβ₄₀ seeds changed from fibrils to spherical aggregates. Moreover，Aβ₄₀ seeds with two different morphologies both promoted Aβ₄₀ secondary nucleation and eventually induced the formation of typical fibril aggregates rich in β-sheet structure. It is shown that the fibrous seeds had greater impact on Aβ₄₀ secondary nucleation than the spherical seeds，and they accelerated Aβ₄₀ secondary nucleation in a concentration-dependent manner. It is worth noting that there is a significant difference in the cytotoxicity of Aβ₄₀ aggregates induced by different morphologies of Aβ₄₀ seeds. The comparison shows that the cytotoxicity of Aβ₄₀ aggregates induced by spherical seeds was significantly higher than that induced by fibrous seeds. This work clarified the role of Aβ seeds induced by Cu²⁺ in promoting Aβ aggregation，thus providing a theoretical basis for the design and development of potent inhibitors against Aβ aggregation and cytotoxicity.
Keyword_Chinese:阿尔茨海默病; 淀粉样β蛋白; 铜离子; 种子; 二次成核
Keywords_English:Alzheimer’s disease; amyloid β-protein(Aβ); copper ions; seed; secondary nucleation

PDF全文下载地址:http://xbzrb.tju.edu.cn/#/digest?ArticleID=6147