In Situ Measurements of the Formation and Morphology of Intracellular 尾-Amyloid Fibrils by Super-Resolution Fluorescence Imaging

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• 作者：Gabriele S. Kaminski Schierle ; Sebastian van de Linde ; Miklos Erdelyi ; Elin K. Esbj枚rner ; Teresa Klein ; Eric Rees ; Carlos W. Bertoncini ; Christopher M. Dobson ; Markus Sauer ; Clemens F. Kaminski
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：August 24, 2011
• 年：2011
• 卷：133
• 期：33
• 页码：12902-12905
• 全文大小：807K
• 年卷期：v.133,no.33(August 24, 2011)
• ISSN：1520-5126

文摘

Misfolding and aggregation of peptides and proteins is a characteristic of many neurodegenerative disorders, including Alzheimer鈥檚 disease (AD). In AD the 尾-amyloid peptide (A尾) aggregates to form characteristic fibrillar structures, which are the deposits found as plaques in the brains of patients. We have used direct stochastic optical reconstruction microscopy, dSTORM, to probe the process of in situ A尾 aggregation and the morphology of the ensuing aggregates with a resolution better than 20 nm. We are able to distinguish different types of structures, including oligomeric assemblies and mature fibrils, and observe a number of morphological differences between the species formed in vitro and in vivo, which may be significant in the context of disease. Our data support the recent view that intracellular A尾 could be associated with A尾 pathogenicity in AD, although the major deposits are extracellular, and suggest that this approach will be widely applicable to studies of the molecular mechanisms of protein deposition diseases.