Aβ-globulomers are formed independently of the fibril pathway
Aβ-globulomers are formed independently of the fibril pathway
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DOI：
10.1016/j.nbd.2008.01.010
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发表时间：
2008-05-01
影响因子：
6.1
通讯作者：
Barghorn, Stefan
中科院分区：
文献类型：
--
作者：
Gellermann, Gerald P.;Byrnes, Helga;Barghorn, Stefan
可溶性A β-寡聚体目前被讨论为阿尔茨海默病（AD）发展的主要致病物种。因此，β-淀粉样蛋白级联假说被A β-寡聚体及其在AD中的中枢神经致病作用所扩展。然而，A β-寡聚体的分子结构及其与淀粉样纤维形成的关系仍然难以捉摸。先前我们证明，A β（1-42）与SDS或脂肪酸孵育诱导形成均匀的球状A β-寡聚体，称为A β-globulomer。在这项研究中，我们研究了A β-球聚体在A β-肽聚集途径中的作用。我们使用体外试验，如硫磺素-T结合和聚集抑制剂如刚果红，以揭示A β-球聚体构象的A β-肽是一种结构实体，其独立于淀粉样蛋白原纤维形成。此外，细胞阿尔茨海默病样斑块形成测定显示A β-球聚体对作为淀粉样斑块沉积的抗性。我们假设A β的构象转换是原纤维形成或A β-球聚体形成的决定性因素。(c)2008年爱思唯尔公司All rights reserved.
Soluble A beta-oligomers are currently discussed as the major causative species for the development of Alzheimer's disease (AD). Consequently, the beta-amyloid cascade hypothesis was extended by A beta-oligomers and their central neuropathogenic role in AD. However, the molecular structure of A beta-oligomers and their relation to amyloid fibril formation remains elusive. Previously we demonstrated that incubation of A beta(1-42) with SDS or fatty acids induces the formation of a homogeneous globular A beta-oligomer termed A beta-globulomer. In this study we investigated the role of A beta-globulomers in the aggregation pathway of A beta-peptide. We used in vitro assays such as thioflavin-T binding and aggregation inhibitors like Congo red to reveal that A beta-peptide in its A beta-globulomer conformation is a structural entity which is independent from amyloid fibril formation. In addition, cellular Alzheimer's-like plaque forming assays show the resistance of A beta-globulomers to deposition as amyloid plaques. We hypothesize that a conformational switch of A beta is decisive for either fibril formation or alternatively and independently A beta-globulomer formation. (c) 2008 Elsevier Inc. All rights reserved.