Amyloid plaque structure and cell surface interactions of β-amyloid fibrils revealed by electron tomography.
Amyloid plaque structure and cell surface interactions of β-amyloid fibrils revealed by electron tomography.
复制标题
DOI：
10.1038/srep43577
复制
发表时间：
2017-02-27
影响因子：
4.6
通讯作者：
Fändrich M
中科院分区：
文献类型：
--
作者：
Han S;Kollmer M;Markx D;Claus S;Walther P;Fändrich M
淀粉样蛋白原纤维作为斑块的沉积是几种神经退行性疾病的关键特征，特别是包括阿尔茨海默病。这种疾病的特征是，如果不是诱发的话，由Aβ肽形成的淀粉样蛋白聚集体存款在脑内或对神经元细胞有毒。我们在这里使用扫描透射电子显微镜（STEM）来确定阿尔茨海默病细胞培养模型中Aβ原纤维的原纤维网络结构和相互作用。从Aβ淀粉样蛋白沉积物中获取的STEM图像显示了三种主要类型的纤维网络结构，称为无定形网络、纤维束和淀粉样蛋白星星。所有这三种细胞都被不同类型的脂质内含物浸润，从小尺寸的外泌体样结构（直径50-100 nm）到大尺寸的细胞外囊泡（高达300 nm）。原纤维还表现出与周围细胞的强烈相互作用，使得原纤维束延伸到质膜的管状内陷中。先前发现细胞模型中的淀粉样蛋白形成具有细胞内起源，并且我们在这里表明它在功能上破坏细胞内膜的完整性，因为它导致溶酶体渗漏。这些数据提供了一个机制的链接，以解释为什么细胞内纤维的形成是有毒的细胞。
The deposition of amyloid fibrils as plaques is a key feature of several neurodegenerative diseases including in particular Alzheimer’s. This disease is characterized, if not provoked, by amyloid aggregates formed from Aβ peptide that deposit inside the brain or are toxic to neuronal cells. We here used scanning transmission electron microscopy (STEM) to determine the fibril network structure and interactions of Aβ fibrils within a cell culture model of Alzheimer’s disease. STEM images taken from the formed Aβ amyloid deposits revealed three main types of fibril network structures, termed amorphous meshwork, fibril bundle and amyloid star. All three were infiltrated by different types of lipid inclusions from small-sized exosome-like structures (50–100 nm diameter) to large-sized extracellular vesicles (up to 300 nm). The fibrils also presented strong interactions with the surrounding cells such that fibril bundles extended into tubular invaginations of the plasma membrane. Amyloid formation in the cell model was previously found to have an intracellular origin and we show here that it functionally destroys the integrity of the intracellular membranes as it leads to lysosomal leakage. These data provide a mechanistic link to explain why intracellular fibril formation is toxic to the cell.