Effects of Physical Damage in the Intermediate Phase on the Progression of Amyloid β Fibrillization
Effects of Physical Damage in the Intermediate Phase on the Progression of Amyloid β Fibrillization
复制标题
中期物理损伤对β淀粉样蛋白纤维化进展的影响
DOI：
10.1002/asia.201901193
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Hiroshi Sugiyama
中科院分区：
文献类型：
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作者：
Ryu Tashiro;Hiroaki Taguchi;Kumi Hidaka;Masayuki Endo;Hiroshi Sugiyama
了解淀粉样蛋白沉积进展的机制对于开发在阿尔茨海默病治疗中抑制该过程的方法是重要的。在淀粉样蛋白β原纤维形成的过渡阶段，物理损伤的影响尚不清楚。在这项研究中，我们使用高速原子力显微镜来研究真实的损伤对β淀粉样蛋白中间体的影响。对中间体的物理损害并不抑制，而是促进了纤维化。这种进展伴随着从球状寡聚体到原纤维的形态变化。这些结果表明，中间体的性质，如结构的脆弱性和稳定性，是高度相关的纤维化速率。
Understanding the mechanism responsible for the progression of amyloid deposition is important for developing methods to suppress this process in the treatment of Alzheimer's disease. The effects of physical damage during the transition phase of amyloid β fibril formation are unclear. In this study, we used high‐speed atomic force microscopy to investigate the effects of damage to the intermediates of amyloid β in real time. Physical damage to intermediates did not suppress, but instead promoted fibrillization. This progression was accompanied by morphological changes from globular oligomers to protofibrils. These results suggest that the properties of the intermediates, such as structural fragility and stability, are highly related to the rate of fibrillization.