Conversion of non-fibrillar β-sheet oligomers into amyloid fibrils in Alzheimer's disease amyloid peptide aggregation
Conversion of non-fibrillar β-sheet oligomers into amyloid fibrils in Alzheimer's disease amyloid peptide aggregation
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DOI：
10.1016/j.bbrc.2007.07.082
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发表时间：
2007-10-05
影响因子：
3.1
通讯作者：
Cladera, Josep
中科院分区：
文献类型：
--
作者：
Benseny-Cases, Nuria;Cocera, Mercedes;Cladera, Josep
β（1-40）是淀粉样蛋白斑块中纤维的主要成分之一，淀粉样蛋白斑块是受阿尔茨海默病影响的大脑的标志。已知在形成其中肽采用良好有序的分子间P-折叠结构的淀粉样蛋白原纤维之前，肽单体缔合形成低分子量和高分子量寡聚体。这些低聚物先前已在电子显微镜、AFM和排阻色谱研究中描述。然而，其特定的二级结构尚未完全确定。在浓度依赖性过程（如淀粉样蛋白聚集）中比较聚集和二级结构测定时的一个主要问题是每种类型实验所需的浓度范围不同。在本研究中，我们使用了染料硫磺素T（ThT），傅里叶变换红外光谱，电子显微镜，以结构表征不同的聚集物种，在A β（1-40）原纤维形成过程中形成。使用含有90 μ M肽的独特样品。结果表明，在聚集动力学的滞后阶段形成的低聚物物种是无序的，螺旋状的，和分子间的非纤维状P-结构的混合物。低聚物的数量和非纤维状β-结构的量在整个迟滞期增长，并且在伸长期期间，这些非纤维状β-结构转化为纤维状（淀粉样蛋白）β-结构，通过高分子量中间体的缔合形成。(C)2007年爱思唯尔公司All rights reserved.
A beta(1-40) is one of the main components of the fibrils found in amyloid plaques, a hallmark of brains affected by Alzheimer's disease. It is known that prior to the formation of amyloid fibrils in which the peptide adopts a well-ordered intermolecular P-sheet structure, peptide monomers associate forming low and high molecular weight oligomers. These oligomers have been previously described in electron microscopy, AFM, and exclusion chromatography studies. Their specific secondary structures however, have not yet been well established. A major problem when comparing aggregation and secondary structure determinations in concentration-dependent processes such as amyloid aggregation is the different concentration range required in each type of experiment. In the present study we used the dye Thioflavin T (ThT), Fourier-transform infrared spectroscopy, and electron microscopy in order to structurally characterize the different aggregated species which form during the A beta(1-40) fibril formation process. A unique sample containing 90 PM peptide was used. The results show that oligomeric species which form during the lag phase of the aggregation kinetics are a mixture of unordered, helical, and intermolecular non-fibrillar P-structures. The number of oligomers and the amount of non-fibrillar beta-structures grows throughout the lag phase and during the elongation phase these non-fibrillar beta-structures are transformed into fibrillar (amyloid) beta-structures, formed by association of high molecular weight intermediates. (C) 2007 Elsevier Inc. All rights reserved.