Conformation dependent monoclonal antibodies distinguish different replicating strains or conformers of prefibrillar Aβ oligomers.
Conformation dependent monoclonal antibodies distinguish different replicating strains or conformers of prefibrillar Aβ oligomers.
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DOI：
10.1186/1750-1326-5-57
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发表时间：
2010-12-13
影响因子：
15.1
通讯作者：
Glabe C
中科院分区：
文献类型：
--
作者：
Kayed R;Canto I;Breydo L;Rasool S;Lukacsovich T;Wu J;Albay R 3rd;Pensalfini A;Yeung S;Head E;Marsh JL;Glabe C
与神经退行性疾病相关的神经退行性疾病共有许多重要的病理特征，例如错误折叠的蛋白质作为淀粉样蛋白寡聚体和原纤维的积累。最近的证据表明，可溶性淀粉样蛋白低聚物，而不是不溶性淀粉样蛋白原纤维可能代表蛋白质聚集体的主要病理种类。我们已经生产了几种单克隆抗体，其特异性识别前原纤维寡聚体，而不识别淀粉样原纤维、单体或天然折叠蛋白。与多克隆抗血清一样，单个单克隆抗体识别不依赖于特定线性氨基酸序列的通用表位，但它们对不同的前原纤维寡聚体子集显示出不同的偏好。对许多不同的前原纤维Aβ寡聚体制剂的免疫学分析表明，Aβ前原纤维寡聚体中存在结构多态性，可根据其与单克隆抗体的反应性进行区分。Western印迹分析表明，单克隆抗体所定义的构象异构体具有不同的大小分布，表明寡聚体结构随大小而变化。不同构象类型的Aβ前原纤低聚物可以作为单体加成的模板，表明它们将Aβ单体转化为更多相同类型的前原纤低聚物。这些结果表明，存在能够接种自身复制的前原纤维Aβ寡聚体的不同结构变体或构象异构体。这些构象异构体可能类似于朊病毒的不同菌株。
Age-related neurodegenerative diseases share a number of important pathological features, such as accumulation of misfolded proteins as amyloid oligomers and fibrils. Recent evidence suggests that soluble amyloid oligomers and not the insoluble amyloid fibrils may represent the primary pathological species of protein aggregates. We have produced several monoclonal antibodies that specifically recognize prefibrillar oligomers and do not recognize amyloid fibrils, monomer or natively folded proteins. Like the polyclonal antisera, the individual monoclonals recognize generic epitopes that do not depend on a specific linear amino acid sequence, but they display distinct preferences for different subsets of prefibrillar oligomers. Immunological analysis of a number of different prefibrillar Aβ oligomer preparations show that structural polymorphisms exist in Aβ prefibrillar oligomers that can be distinguished on the basis of their reactivity with monoclonal antibodies. Western blot analysis demonstrates that the conformers defined by the monoclonal antibodies have distinct size distributions, indicating that oligomer structure varies with size. The different conformational types of Aβ prefibrillar oligomers can serve as they serve as templates for monomer addition, indicating that they seed the conversion of Aβ monomer into more prefibrillar oligomers of the same type. These results indicate that distinct structural variants or conformers of prefibrillar Aβ oligomers exist that are capable of seeding their own replication. These conformers may be analogous to different strains of prions.
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影响因子：
15.1
作者：
Kayed R;Head E;Sarsoza F;Saing T;Cotman CW;Necula M;Margol L;Wu J;Breydo L;Thompson JL;Rasool S;Gurlo T;Butler P;Glabe CG
通讯作者：
Glabe CG
影响因子：
64.8
作者：
Toyama, Brandon H.;Kelly, Mark J. S.;Weissman, Jonathan S.
通讯作者：
Weissman, Jonathan S.
影响因子：
5.3
作者：
Baglioni, Serena;Casamenti, Fiorella;Stefani, Massimo
通讯作者：
Stefani, Massimo
影响因子：
4.8
作者：
Gerber, Remo;Tahiri-Alaoui, Abdessamad;James, William
通讯作者：
James, William
DOI：
10.1073/pnas.0609638103
发表时间：
2006-12-26
影响因子：
11.1
作者：
Shewmaker, Frank;Wickner, Reed B.;Tycko, Robert
通讯作者：
Tycko, Robert