Internalisation and toxicity of amyloid‐β 1‐42 is influenced by its conformation and assembly state rather than size,FEBS Letters

当前位置： X-MOL 学术 › FEBS Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Internalisation and toxicity of amyloid‐β 1‐42 is influenced by its conformation and assembly state rather than size
FEBS Letters ( IF 3.0 ) Pub Date : 2020-09-11 , DOI: 10.1002/1873-3468.13919
Devkee M Vadukul _{1,

2} , Mahmoud Maina _{1,

3} , Hannah Franklin ₁ , Astrid Nardecchia ₁ , Louise C Serpell ₁ , Karen E Marshall ₁

Affiliation

Amyloid fibrils found in plaques in Alzheimer’s disease (AD) brains are composed of amyloid‐β peptides. Oligomeric amyloid‐β 1‐42 (Aβ42) is thought to play a critical role in neurodegeneration in AD. Here, we determine how size and conformation affect neurotoxicity and internalisation of Aβ42 assemblies using biophysical methods, immunoblotting, toxicity assays and live‐cell imaging. We report significant cytotoxicity of Aβ42 oligomers and their internalisation into neurons. In contrast, Aβ42 fibrils show reduced internalisation and no toxicity. Sonicating Aβ42 fibrils generates species similar in size to oligomers but remains nontoxic. The results suggest that Aβ42 oligomers have unique properties that underlie their neurotoxic potential. Furthermore, we show that incubating cells with Aβ42 oligomers for 24 h is sufficient to trigger irreversible neurotoxicity.

中文翻译：

β-淀粉样蛋白 1-42 的内化和毒性受其构象和组装状态的影响，而不是大小

在阿尔茨海默病 (AD) 大脑的斑块中发现的淀粉样蛋白原纤维由淀粉样蛋白-β 肽组成。低聚淀粉样蛋白-β 1-42 (Aβ42) 被认为在 AD 的神经变性中起关键作用。在这里，我们使用生物物理方法、免疫印迹、毒性测定和活细胞成像来确定大小和构象如何影响 Aβ42 组装体的神经毒性和内化。我们报告了 Aβ42 寡聚体的显着细胞毒性及其向神经元的内化作用。相反，Aβ42 原纤维显示内化减少且无毒性。超声处理 Aβ42 原纤维会产生大小与低聚物相似但仍然无毒的物质。结果表明，Aβ42 寡聚体具有独特的特性，是其神经毒性潜力的基础。此外，

更新日期：2020-09-11

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11