Studies on the molecular mechanism of amyloid fibril formation and on the role of extracellular quality control mechanism in the fibril formation.

我们在体外构建了几个淀粉样原纤维形成系统，以评估各种生物分子或反应条件在淀粉样原纤维形成中的作用。本研究的主要发现如下：(1)在中性pH条件下，非酯化脂肪酸在体外可诱导β-2-微球蛋白淀粉原纤维的伸长。(2)空气-水界面、搅拌和A-β多肽浓度在阿尔茨海默病β-淀粉样原纤维成核过程中起关键作用。(3)阐明了人血浆蛋白和胞外分子伴侣α_2-巨球蛋白抑制β_2-微球蛋白淀粉样原纤维形成的详细分子机制。

We constructed several amyloid fibril formation system in vitro to evaluate the roles of the various biological molecules or reaction conditions in the amyloid fibril formation. The key findings of this study are as follows : (1) Non-esterified fatty acids induce the extension of β2-microglobulin amyloid fibril at a neutral pH in vitro. (2) Air-water interface, agitation and concentrations of Aβ peptide play critical roles in the nucleation of β-amyloid fibril of Alzheimer's disease. (3) The detailed molecular mechanismof α2-macroglobulin, a human plasma protein and an extracellular molecular chaperon, in the inhibition of β2-microglobulin amyloid fibril formation was clarified.