In Situ Measurements of the Formation and Morphology of Intracellular β-Amyloid Fibrils by Super-Resolution Fluorescence Imaging
In Situ Measurements of the Formation and Morphology of Intracellular β-Amyloid Fibrils by Super-Resolution Fluorescence Imaging
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DOI：
10.1021/ja201651w
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发表时间：
2011-08-24
影响因子：
15
通讯作者：
Kaminski, Clemens F.
中科院分区：
文献类型：
--
作者：
Schierle, Gabriele S. Kaminski;van de Linde, Sebastian;Kaminski, Clemens F.
肽和蛋白质的错误折叠和聚集是包括阿尔茨海默病（AD）在内的许多神经退行性疾病的特征。在AD中，P-淀粉样肽（A β）聚集形成特征性纤维状结构，其是在患者脑中发现的斑块状沉积物。我们已经使用直接随机光学重建显微镜，dSTORM，探测原位A β聚集的过程和随后的聚集体的形态，分辨率优于20 nm。我们能够区分不同类型的结构，包括寡聚体组装和成熟的原纤维，并观察到在体外和体内形成的物种之间的许多形态学差异，这在疾病的背景下可能是显着的。我们的数据支持最近的观点，细胞内A β可能与A β致病性AD，虽然主要存款是细胞外，并建议这种方法将被广泛适用于蛋白质沉积疾病的分子机制的研究。
Misfolding and aggregation of peptides and proteins is a characteristic of many neurodegenerative disorders, including Alzheimer's disease (AD). In AD the P-amyloid peptide (A beta) 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 beta 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 beta could be associated with A beta 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.