Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan.
Biomedical Research Institute, AIST, Ibaraki, 305-8566, Japan.
Chembiochem. 2018 Mar 2;19(5):430-433. doi: 10.1002/cbic.201700576. Epub 2018 Jan 19.
The formation of neurotoxic aggregates by amyloid-β peptide (Aβ) is considered to be a key step in the onset of Alzheimer's disease. It is widely accepted that oligomers are more neurotoxic than amyloid fibrils in the aqueous-phase aggregation of Aβ. Membrane-mediated amyloidogenesis is also relevant to the pathology, although the relationship between the aggregate size and cytotoxicity has remained elusive. Here, aggregation processes of Aβ on living cells and cytotoxic events were monitored by fluorescence techniques. Aβ formed amyloids after forming oligomers composed of ≈10 Aβ molecules. The formation of amyloids was necessary to activate apoptotic caspase-3 and reduce the ability of the cell to proliferate; this indicated that amyloid formation is a key event in Aβ-induced cytotoxicity.
淀粉样蛋白-β 肽 (Aβ) 形成神经毒性聚集体被认为是阿尔茨海默病发病的关键步骤。广泛接受的观点是，在 Aβ 的水相聚集过程中，寡聚体比淀粉样纤维更具神经毒性。尽管聚集物大小与细胞毒性之间的关系仍不清楚，但膜介导的淀粉样生成也与病理学相关。在这里，通过荧光技术监测 Aβ 在活细胞上的聚集过程和细胞毒性事件。Aβ 在形成由 ≈10 个 Aβ 分子组成的寡聚体后形成淀粉样纤维。淀粉样纤维的形成是激活凋亡半胱氨酸蛋白酶-3 和降低细胞增殖能力所必需的；这表明淀粉样形成是 Aβ 诱导细胞毒性的关键事件。
