Human Health Therapeutics, National Research Council of Canada, Ottawa, Ontario, Canada.
Human Health Therapeutics, National Research Council of Canada, Ottawa, Ontario, Canada.
Biochem Biophys Res Commun. 2014 Mar 14;445(3):656-60. doi: 10.1016/j.bbrc.2014.02.064. Epub 2014 Feb 22.
The synthetic ~5 kDa ABP (amyloid-ß binding peptide) consists of a region of the 228 kDa human pericentrioloar material-1 (PCM-1) protein that selectively and avidly binds in vitro Aβ1-42 oligomers, believed to be key co-drivers of Alzheimer's disease (AD), but not monomers (Chakravarthy et al., (2013) [3]). ABP also prevents Aß1-42 from triggering the apoptotic death of cultured human SHSY5Y neuroblasts, likely by sequestering Aß oligomers, suggesting that it might be a potential AD therapeutic. Here we support this possibility by showing that ABP also recognizes and binds Aβ1-42 aggregates in sections of cortices and hippocampi from brains of AD transgenic mice and human AD patients. More importantly, ABP targets Aβ1-42 aggregates when microinjected into the hippocampi of the brains of live AD transgenic mice.
该合成~5 kDa ABP（淀粉样蛋白-β结合肽）由人中心体周围物质-1（PCM-1）蛋白的 228 kDa 区域组成，该区域选择性且强烈地结合体外 Aβ1-42 寡聚体，被认为是阿尔茨海默病（AD）的关键协同驱动因素，但不与单体结合（Chakravarthy 等人，（2013）[3]）。ABP 还可以防止 Aβ1-42 触发培养的人 SHSY5Y 神经母细胞瘤的凋亡死亡，可能是通过隔离 Aβ 寡聚体，这表明它可能是一种潜在的 AD 治疗方法。在这里，我们通过显示 ABP 还可以识别和结合 AD 转基因小鼠和人类 AD 患者大脑皮质和海马体切片中的 Aβ1-42 聚集体来支持这种可能性。更重要的是，当将 ABP 微注射到活 AD 转基因小鼠大脑的海马体中时，它会靶向 Aβ1-42 聚集体。
