The two most common aging-related diseases, Alzheimer’s disease and type 2 diabetes mellitus, are associated with accumulation of amyloid proteins (β-amyloid and amylin, respectively). This amylin aggregation is reportedly cytotoxic to neurons. We found that aggregation of human amylin (hAmylin) induced neuronal apoptosis without obvious microglial infiltration in vivo. High concentrations of hAmylin irreversibly aggregated on the surface of the neuronal plasma membrane. Long-term incubation with hAmylin induced morphological changes in neurons. Moreover, hAmylin permeabilized the neuronal membrane within 1 min in a manner similar to Triton X-100, allowing impermeable fluorescent antibodies to enter the neurons and stain intracellular antigens. hAmylin also permeabilized the cell membrane of astrocytes, though more slowly. Under scanning electron microscopy, we observed that hAmylin destroyed the integrity of the cell membranes of both neurons and astrocytes. Additionally, it increased intracellular reactive oxygen species generation and reduced the mitochondrial membrane potential. Thus, by aggregating on the surface of neurons, hAmylin impaired the cell membrane integrity, induced reactive oxygen species production, reduced the mitochondrial membrane potential, and ultimately induced neuronal apoptosis.

中文翻译：

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人胰淀素对大鼠原代海马神经元膜稳定性的影响。

两种最常见的衰老相关疾病，阿尔茨海默病和 2 型糖尿病，与淀粉样蛋白（分别为 β-淀粉样蛋白和淀粉样蛋白）的积累有关。据报道，这种胰淀素聚集对神经元具有细胞毒性。我们发现人胰岛淀粉样多肽（hAmylin）的聚集诱导了神经元凋亡，体内没有明显的小胶质细胞浸润。. 高浓度的 hAmylin 不可逆地聚集在神经元质膜表面。与 hAmylin 长期孵育诱导神经元的形态变化。此外，hAmylin 以类似于 Triton X-100 的方式在 1 分钟内渗透神经元膜，允许不可渗透的荧光抗体进入神经元并染色细胞内抗原。hAmylin 也可渗透星形胶质细胞的细胞膜，但速度较慢。在扫描电子显微镜下，我们观察到 hAmylin 破坏了神经元和星形胶质细胞的细胞膜的完整性。此外，它增加了细胞内活性氧的产生并降低了线粒体膜电位。因此，通过在神经元表面聚集，hAmylin 损害了细胞膜的完整性，