Selenium-Enhanced Electron Microscopic Imaging of Different Aggregate Forms of a Segment of the Amyloid 尾 Peptide in Cells
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- 作者：Eva K. McGuire ; Michael Motskin ; Benedetta Bolognesi ; Shane D. Bergin ; Tuomas P. J. Knowles ; Jeremy Skepper ; Leila M. Luheshi ; David W. McComb ; Christopher M. Dobson ; Alexandra E. Porter
- 刊名：ACS Nano
- 出版年：2012
- 出版时间：June 26, 2012
- 年：2012
- 卷：6
- 期：6
- 页码：4740-4747
- 全文大小：601K
- 年卷期：v.6,no.6(June 26, 2012)
- ISSN：1936-086X
文摘
The aggregation of misfolded proteins is a common feature underlying a wide range of age-related degenerative disorders, including Alzheimer鈥檚 and Parkinson鈥檚 diseases. A key aspect of understanding the molecular origins of these conditions is to define the manner in which specific types of protein aggregates influence disease pathogenesis through their interactions with cells. We demonstrate how selenium-enhanced electron microscopy (SE-EM), combined with tomographic reconstruction methods, can be used to image, here at a resolution of 5鈥?0 nm, the interaction with human macrophage cells of amyloid aggregates formed from A尾25鈥?6, a fragment of the A尾 peptide whose self-assembly is associated with Alzheimer鈥檚 disease. We find that prefibrillar aggregates and mature fibrils are distributed into distinct subcellular compartments and undergo varying degrees of morphological change over time, observations that shed new light on the origins of their differential toxicity and the mechanisms of their clearance. In addition, the results show that SE-EM provides a powerful and potentially widely applicable means to define the nature and location of protein assemblies in situ and to provide detailed and specific information about their partitioning and processing.