Wang Chen-Wei, Nan Dou-Dou, Wang Xin-Meng, Ke Zun-Ji, Chen Guo-Jun, Zhou Jiang-Ning
CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230026, China.
Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Sci Bull (Beijing). 2017 Dec 15;62(23):1593-1601. doi: 10.1016/j.scib.2017.11.005. Epub 2017 Nov 10.
In vivo monitoring neuropathological changes in Alzheimer's disease (AD) animal model is critical for drug development. Here, by integrating blood-brain barrier penetrable peptide, we have developed a peptide probe which based on angiopep-2. Angiopep-based probe exhibited high binding affinity to Aβ aggregates and labeled senile plaques in vivo. Remarkably, the in vivo near-infrared imaging data revealed that fluorescence signals of this probe were nearly 3-fold higher in the brains of 16-month-old APP/PS1 transgenic mice compared to C57 mice and exhibited linear correlation with the senile plaques load process in 4-, 8-, 16-month-old APP/PS1 transgenic mice. Moreover, senile plaques load was detected in vivo as early as 4 months of age that even at the very beginning of plaques developed in APP/PS1 transgenic mice. Taken together, this novel peptide-based probe achieved dynamic monitoring senile plaques in APP/PS1 transgenic mice and have been ready to use in drug development in AD mouse model.
在阿尔茨海默病（AD）动物模型中对神经病理变化进行体内监测对于药物开发至关重要。在此，通过整合血脑屏障可穿透肽，我们基于血管活性肠肽-2开发了一种肽探针。基于血管活性肠肽的探针在体内对Aβ聚集体表现出高结合亲和力并标记老年斑。值得注意的是，体内近红外成像数据显示，与C57小鼠相比，该探针在16个月大的APP/PS1转基因小鼠大脑中的荧光信号高出近3倍，并且在4、8、16个月大的APP/PS1转基因小鼠中与老年斑负荷过程呈线性相关。此外，早在4个月大时就在体内检测到老年斑负荷，甚至在APP/PS1转基因小鼠斑块形成的最初阶段。综上所述，这种新型基于肽的探针实现了对APP/PS1转基因小鼠老年斑的动态监测，并已准备好在AD小鼠模型的药物开发中使用。
