Preparation of pure populations of covalently stabilized amyloid β-protein oligomers of specific sizes

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• 作者：Eric Y. Hayden ; Joseph L. Conovaloff ; Ashley Mason ; Gal Bitan ; David B. Teplow ; ^{dteplow@mednet.ucla.edu}
• 关键词：Alzheimer's disease ; Amyloid β-protein ; Oligomers ; Isolation ; Protein structure ; Protein function
• 刊名：Analytical Biochemistry
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：518
• 期：Complete
• 页码：78-85
• 全文大小：1162 K
• 卷排序：518

文摘

Evidence suggests that amyloid β-protein (Aβ) oligomers may be seminal pathogenic agents in Alzheimer's disease (AD). If so, developing oligomer-targeted therapeutics requires an understanding of oligomer structure. This has been difficult due to the instability of these non-covalently associated Aβ assemblies. We previously used rapid, zero-length, in situ chemical cross-linking to stabilize oligomers of Aβ40. These enabled us to isolate pure, stable populations of dimers, trimers, and tetramers and to determine their structure-activity relationships. However, equivalent methods applied to Aβ42 did not produce stable oligomers. We report here that the use of an Aβ42 homologue, [F10, Y42]Aβ42, coupled with sequential denaturation/dissociation and gel electrophoresis procedures, provides the means to produce highly pure, stable populations of oligomers of sizes ranging from dimer through dodecamer that are suitable for structure-activity relationship determination.