Chun Yoon Sun, Kwon Oh-Hoon, Oh Hyun Geun, Cho Yoon Young, Yang Hyun Ok, Chung Sungkwon
Department of Physiology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.
Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea.
Biomol Ther (Seoul). 2019 May 1;27(3):276-282. doi: 10.4062/biomolther.2018.112.
β-amyloid precursor protein (APP) can be cleaved by α-, and γ-secretase at plasma membrane producing soluble ectodomain fragment (sAPPα). Alternatively, following endocytosis, APP is cleaved by β-, and γ-secretase at early endosomes generating β-amyloid (Aβ), the main culprit in Alzheimer's disease (AD). Thus, APP endocytosis is critical for Aβ production. Recently, we reported that , the indigenous vegetables consumed in Tanzania, improved cognitive function and decreased Aβ production. In this study, we examined the underlying mechanism of justicidin A, the active compound of , on Aβ production. We found that justicidin A reduced endocytosis of APP, increasing sAPPα level, while decreasing Aβ level in HeLa cells overexpressing human APP with the Swedish mutation. The effect of justicidin A on Aβ production was blocked by endocytosis inhibitors, indicating that the decreased APP endocytosis by justicidin A is the underlying mechanism. Thus, justicidin A, the active compound of , may be a novel agent for AD treatment.
β-淀粉样前体蛋白（APP）可在质膜上被α-分泌酶和γ-分泌酶切割，产生可溶性胞外域片段（sAPPα）。另外，内吞作用后，APP在早期内体中被β-分泌酶和γ-分泌酶切割，产生β-淀粉样蛋白（Aβ），这是阿尔茨海默病（AD）的主要致病因素。因此，APP内吞作用对于Aβ的产生至关重要。最近，我们报道了坦桑尼亚食用的本土蔬菜改善了认知功能并减少了Aβ的产生。在本研究中，我们研究了坦桑尼亚本土蔬菜中的活性化合物正义霉素A对Aβ产生的潜在机制。我们发现正义霉素A减少了APP的内吞作用，增加了sAPPα水平，同时降低了过表达带有瑞典突变的人APP的HeLa细胞中的Aβ水平。内吞作用抑制剂阻断了正义霉素A对Aβ产生的影响，表明正义霉素A降低APP内吞作用是其潜在机制。因此，坦桑尼亚本土蔬菜中的活性化合物正义霉素A可能是一种治疗AD的新型药物。
