Protein-protein interactions in amyloid deposits

一些与年龄相关的疾病，如II型糖尿病、阿尔茨海默氏症和帕金森氏病，都是特定蛋白质聚集形成不溶性淀粉样纤维的特征。在体内，淀粉样蛋白沉积还含有三种重要的非纤维蛋白成分，即血清淀粉样蛋白P组分、载脂蛋白E和α1-抗糜蛋白酶。这些非纤维淀粉样组分与各种各样的淀粉样原纤维结合，而与蛋白质组分的性质无关。本研究旨在确定这种识别过程的结构基础、非纤维成分使淀粉样蛋白纤维形成网络的能力，以及这些相互作用对淀粉样蛋白纤维细胞毒性的影响。

The aggregation of specific proteins to form insoluble amyloid fibrils is characteristic of several age-related diseases such as type-II diabetes, Alzheimer's disease and Parkinson's disease. In vivo amyloid deposits also contain three prominent non-fibrillar protein components, namely serum amyloid P component, apolipoprotein E and alpha1-antichymotrypsin. These non-fibrillar amyloid components bind to a wide variety of amyloid fibrils, irrespective of the nature of the protein constituent. This proposal is to identify the structural basis for this recognition process, the capacity of non-fibrillar components to cross-link amyloid fibrils to form networks and the influence of these interactions on amyloid fibril cytotoxicity.