Elucidation and control of the molecular mechanism of amyloid fibril formation Applications for nano materials

阐明和控制淀粉样原纤维形成的分子机制纳米材料的应用

基本信息

批准号：
15602001
负责人：
HASEGAWA Kazuhiro
金额：
$ 2.3万
依托单位：
University of Fukui (2004)福井医科大学 (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

The aims of this study are (1) establishment of general molecular model of amyloid fibril formation and dissociation via the study of beta-amyloid and beta2-microglobulin (β2-m) amyloid (2) elucidation of the effect of various biological molecules or chemical compounds on the common pathogenesis of each amyloidosis, and suggest a strategy for treatment (3) invention of the control method for the formation and dissociation of amyloid fibril, and their application to nanotechnology. Results : (1) six peptides correspond to six of the seven beta sheet in the native structure of β2-m, and examined their amyloidogenisity. Among the peptides examined, peptide(21-31) showed fibril formation. (2) in β2-m amyloid fibril formation, partial unfolding of β2-m is believed to be prerequisite to its assembly into Aβ2M amyloid fibrils. In this study, low concentrations of trifluoroethanol and sodium dodecyl sulfate was found to induce the amyloidogenic partial unfolding of β2-m and result in the extension of Aβ2M amyloid fibrils at a neutral pH. (3) Polyphenols or vitamin A related compounds are found to inhibit the fibril formation of β-amyloid fibrils and to destabilize the preformed fibrils in vitro. (4) a direct thermodynamic analysis of amyloid fibril formation using isothermal titration calorimetry was develpoed. This investigation enables us to measure the heat capacity and enthalpy, and to estimate the stability and structural information on the conformational change of amyloidogenic proteins during fibril formation. As the conclusion of this study, remarkable advance on the clarification of the molecular mechanism of fibril formation in vitro was obtained. Furthermore, useful characteristics of amyloid fibril formation and dissociation for the application to nanotechnology were discovered.

The aims of this study are (1) establishment of general molecular model of amyloid fibril formation and dissociation via the study of beta-amyloid and beta2-microglobulin (β2-m) amyloid (2) elucidation of the effect of various biological molecules or chemical compounds on the common pathogenesis of each amyloidosis, and suggest a strategy for treatment (3) accident of the control method for the淀粉样蛋白原纤维的形成和解离，及其在纳米技术中的应用。结果：（1）六个宠物对应于β2-M天然结构中七个β板中的六个，并检查了它们的淀粉样蛋白异生。在检查的宠物中，肽（21-31）显示了原纤维形成。（2）在β2-m淀粉样蛋白原纤维形成中，β2-m的部分展开被认为是将其组装到Aβ2M淀粉样蛋白原纤维中的先决条件。在这项研究中，发现低浓度的三氟乙醇和十二烷基硫酸钠会诱导β2-M的淀粉样蛋白生成部分展开，并导致中性pH值的Aβ2M淀粉样蛋白纤维扩展。（3）发现多酚或维生素A相关化合物可抑制β-淀粉样纤维原纤维的原纤维形成，并在体外破坏预先形成的原纤维。（4）使用等温滴定量热法对淀粉样蛋白原纤维形成的直接热力学分析被取代。这项投资使我们能够衡量热容量和焓，并估计纤维形成过程中淀粉样蛋白会议变化的稳定性和结构信息。作为这项研究的结论，可以在体外阐明原纤维形成的分子机理方面的显着进步。此外，还发现了淀粉样蛋白原纤维形成和分离纳米技术的有用特征。