Systemic analysis of amyloidosis using animal models

淀粉样变性是一种蛋白质结构紊乱，其特征是由异常构象变化引起的不溶性淀粉样原纤维的细胞外沉积。我们已经开发了一种新的分析系统，用于在试管中从合成肽形成淀粉样纤维，并开发了几种新的小鼠品系，用于研究各种淀粉样变性。利用这些体外和体内系统，对淀粉样变性进行系统分析，以阐明淀粉样变性传播的发病机制。我们发现了1）通过粪便和骨骼肌的新传播途径，2）新的治疗靶点，包括抑制纤维形成的肽、热休克转录因子1（HSF 1）和载脂蛋白A-I，以及3）几种新开发的用于淀粉样变性研究的可变小鼠品系。

Amyloidoses are protein structural disorders characterized by the extracellular deposition of insoluble amyloid fibrils resulting from abnormal conformational changes. We have developed a new analytical system for amyloid fibril formation from synthetic peptides in test tubes and several new mouse strains for studying various kinds of amyloidoses. Using these in vitro and in vivo systems, systemic analysis of amyloidosis was performed to elucidate the pathogenesis of transmission of amyloidosis. We found 1) new transmission routes through feces and skeletal muscle, 2) new therapeutic targets including peptides inhibiting fibril formation, heat shock transcription factor 1 (HSF1) and apolipoprotein A-I, and 3) several newly developed mouse strains variable for amyloidosis researches.