Cortijo-Arellano Marta, Ponce Jovita, Durany Núria, Cladera Josep
Biophysics Unit and Centre of Studies in Biophysics, Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, 08193 Bellaterra, Spain.
Biochem Biophys Res Commun. 2008 Apr 4;368(2):238-42. doi: 10.1016/j.bbrc.2008.01.049. Epub 2008 Jan 18.
Amyloid fibrils are a hallmark of Alzheimer's and prion diseases. In both pathologies fibrils are found associated to glycosaminoglycans, modulators of the aggregation process. Amyloid peptides and proteins with very poor sequence homologies originate very similar aggregates. This implies the possible existence of a common formation mechanism. A homologous structural motif has recently been described for the Alzheimer's peptide Abeta(1-28) and the prion protein fragment PrP(185-208). We have studied the influence histidine residues and heparin on the aggregation process of both peptides and determined the possible amyloid characteristics of PrP(185-208), still unknown. The results show that PrP(185-208) forms amyloid aggregates in the presence of heparin. Histidines influence the aggregation kinetics, as in Abeta(1-28), although to a lesser extent. Other spectroscopic properties of the PrP(185-208) fragment are shown to be equivalent to those of other amyloid peptides and PrP(185-208) is shown to be cytotoxic using a neuroblastoma cell line.
淀粉样纤维是阿尔茨海默病和朊病毒疾病的一个标志。在这两种病理状态下，都发现纤维与糖胺聚糖有关，糖胺聚糖是聚集过程的调节剂。氨基酸序列同源性极低的淀粉样肽和蛋白质却能形成非常相似的聚集体。这意味着可能存在一种共同的形成机制。最近已描述了阿尔茨海默病肽β-淀粉样蛋白（1-28）和朊病毒蛋白片段PrP（185-208）具有同源结构基序。我们研究了组氨酸残基和肝素对这两种肽聚集过程的影响，并确定了PrP（185-208）可能的淀粉样特征，其特征仍不为人知。结果表明，PrP（185-208）在肝素存在的情况下形成淀粉样聚集体。与β-淀粉样蛋白（1-28）一样，组氨酸影响聚集动力学，不过程度较小。PrP（185-208）片段的其他光谱性质与其他淀粉样肽的光谱性质相当，并且使用神经母细胞瘤细胞系显示PrP（185-208）具有细胞毒性。
